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Buckley, Rebecca Hatcher

Overview:

The overall emphasis of Dr. Buckley's research is in human T,B and NK cell development and in aberrations in their development and regulation. The work involves three particular areas of investigation: 1) the cellular and molecular bases of genetically-determined human immunodeficiency diseases, 2) the use of bone marrow stem cells to cure genetically-determined immunodeficiency diseases, and 3) the use of human SCID bone marrow stem cell chimeras to study human thymic education, T and B cell ontogeny, tolerance induction and MHC restriction mechanisms. Methodology includes monoclonal antibody (mAb) analyses of lymphocyte phenotypes, a variety of T cell and natural killer (NK) cell functional assays, studies of thymic output by T cell receptor recombination excision circle measurement, studies of T cell diversity by spectratyping, studies of T cell longevity by telomere analysis and assessment of B cell differentiation and function. A unique resource available for her studies is the largest populations of patients with genetically-determined immunodeficiency diseases in the U.S., which includes the largest population in the world of longterm SCID chimeras treated at a single center, some of whom have been studied and followed for more than 33 years. The administration of rigorously T cell depleted haploidentical bone marrow stem cells to SCID recipients without pre-transplant conditioning or post-transplant use of immunosuppressive drugs to prevent GVHD provides an unmanipulated system for studying human thymic education, T and B cell ontogeny, MHC restriction mechanisms and tolerance induction. Studies to identify mutations in patients with primary immunodeficiency are continuing, particularly in those with SCID.

Positions:

James Buren Sidbury Professor of Pediatrics, in the School of Medicine

Pediatrics, Allergy and Immunology
School of Medicine

Professor of Pediatrics

Pediatrics, Allergy and Immunology
School of Medicine

Professor of Immunology in the Department of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1958

M.D. — University of North Carolina at Chapel Hill

News:

Grants:

Prospective Study of SCID Infants who receive Hematopoietic Cell Therapy

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
University of California - San Francisco
Role
Principal Investigator
Start Date
September 01, 2014
End Date
August 31, 2019

Safety and Efficacy of Hizentra in Pediatric BMT

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
Carolinas HealthCare System
Role
Principal Investigator
Start Date
October 18, 2017
End Date
June 30, 2018

Training Program in Inflammatory and Immunological Diseases

Administered By
Medicine, Rheumatology and Immunology
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
September 30, 1980
End Date
August 31, 2017

Identifying the Causes of Primary immunodeficiency through Next Generation Sequencing

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
Baxter Healthcare Corporation
Role
Principal Investigator
Start Date
April 01, 2014
End Date
March 31, 2015

Prospective Study of SCID Infants who receive Hematopoietic Cell Therapy

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
University of California - San Francisco
Role
Principal Investigator
Start Date
September 12, 2009
End Date
August 31, 2014

Identification of Disease-Causing Mutations in SCID Using Exome-Wide Sequencing

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 30, 2009
End Date
August 31, 2012

Mechanisms of Allogeneic Stem Cell Education in SCID

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1999
End Date
June 30, 2012

Development And Persistence Of Immunity In SCID Chimeras

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1998
End Date
April 30, 2010

Mentored Clinical Research Scholar Program

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 30, 2002
End Date
September 29, 2006

Research Training in Allergy and Clinical Immunology

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1998
End Date
June 30, 2000

Mechanisms And Therapy Of Primary Immunodeficiency

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1996
End Date
July 31, 1999

Mechanisms And Therapy Of Primary Immunodeficiency

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1995
End Date
July 31, 1999

mechanisms and therapy of primary immunodefficiency

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1995
End Date
July 31, 1999

Research Training In Allergy And Clinical Immunology

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 19, 1907
End Date
June 30, 1999

Center For Developmental Immunology And Host Defense

Administered By
Pediatrics
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 1998

Regulation Of Ige Synthesis By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1997
End Date
March 31, 1998

Regulation Of Human Ige Synthesis By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1996
End Date
March 31, 1998

The Regulation Of Human Ige Syntehsis By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1993
End Date
March 31, 1998

Center For Developmental Immunology And Host Defense

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1992
End Date
August 31, 1997

Haploidentical Stem Cell Education In The Human Thymus

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 1996
End Date
January 31, 1997

The Regulation Of Human 1ge Synthesis By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1989
End Date
August 01, 1994

The Regulation Of Human Ige Syntheses By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1991
End Date
September 30, 1992

The Regulation Of Human Ige Synthesis By Cytokines

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1990
End Date
July 01, 1992

Immunoregulation In Eczema And Other Atopic Diseases

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1986
End Date
August 01, 1991

Immunoregulation In Eczema And Other Atopic Disorders

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1987
End Date
August 01, 1989

Allergy And Clinical Immunology

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1986
End Date
June 01, 1987

Allergy And Clinial Immunology

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 01, 1986
End Date
June 01, 1987

Lymphocyte Responses In Immaturity And Immunodeficiency

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 1986
End Date
January 01, 1987

In Vitro Studies Of Human Ige Synthesis

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 1985
End Date
November 01, 1986

Immunoregulation In Ec\Ema And Other Atopic Diseases

Administered By
Pediatrics, Allergy and Immunology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1985
End Date
August 01, 1986
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Awards:

Member. National Academy of Science.

Type
National
Awarded By
National Academy of Science
Date
January 01, 2011

Member. Institute of Medicine of The National Academies.

Type
National
Awarded By
Institute of Medicine of The National Academies
Date
January 01, 2003

Publications:

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare condition.Data from the USIDNET Registry provide a resource to examine the characteristics of patients with rare immune deficiency diseases.A query was submitted to the USIDNET requesting deidentified data for patients with physician-diagnosed AD-HIES through July 2016.Data on 85 patients diagnosed with AD-HIES (50 males; 35 females) born between 1950 and 2013, collected by 14 physicians from 25 states and Quebec, were entered into the USIDNET Registry by July 2016. Cumulative follow-up was 2157 years. Of these patients, 45.9% had a family history of HIES. The complications reported included skin abscesses (74.4%), eczema (57.7%), retained primary teeth (41.4%), fractures (39%), scoliosis (34.1%), and cancer (7%). Reported allergic diseases included food (37.8%), environmental (18%), and drugs (42.7%). The mean serum IgE level was 8383.7 kU/mL and was inversely correlated to the patient's age. A total of 49.4% had eosinophilia; 56% were known to be on trimethoprim-sulfamethoxazole, 26.6% on antifungal coverage, and 30.6% on immunoglobulin replacement therapy. Pneumonias were more commonly attributed to Staphylococcus aureus (55.3%) or Aspergillus fumigatus (22.4%); 19.5% had a history of lung abscess; these were most often associated with Pseudomonas aeruginosa (P Fisher's exact test = .029) or A. fumigatus (P Fisher's exact test = .016). Lung abscesses were significantly associated with drug reactions (P χ(2) = .01; odds ratio: 4.03 [1.2-12.97]), depression (P Fisher's exact test = .036), and lower Karnofsky index scores (P Mann-Whitney = .007).Data from the USIDNET Registry summarize the currently reported clinical characteristics of a large cohort of subjects with AD-HIES.

Authors
Gernez, Y; Freeman, AF; Holland, SM; Garabedian, E; Patel, NC; Puck, JM; Sullivan, KE; Akhter, J; Secord, E; Chen, K; Buckley, R; Haddad, E; Ochs, HD; Fuleihan, R; Routes, J; Muskat, M; Lugar, P; Mancini, J; Cunningham-Rundles, C
MLA Citation
Gernez, Y, Freeman, AF, Holland, SM, Garabedian, E, Patel, NC, Puck, JM, Sullivan, KE, Akhter, J, Secord, E, Chen, K, Buckley, R, Haddad, E, Ochs, HD, Fuleihan, R, Routes, J, Muskat, M, Lugar, P, Mancini, J, and Cunningham-Rundles, C. "Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry." The journal of allergy and clinical immunology. In practice (September 19, 2017).
PMID
28939137
Source
epmc
Published In
Journal of Allergy and Clinical Immunology: In Practice
Publish Date
2017
DOI
10.1016/j.jaip.2017.06.041

Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT.

Severe combined immunodeficiency (SCID) is effectively treated with hematopoietic cell transplantation (HCT), with overall survival approaching 90% in contemporary reports. However, survivors are at risk for developing late complications because of the variable durability of high-quality immune function, underlying genotype of SCID, comorbidities due to infections in the pretransplantation and post-transplantation periods, and use of conditioning before transplantation. An international group of transplantation experts was convened in 2016 to review the current knowledge of late effects seen in SCID patients after HCT and to develop recommendations for screening and monitoring for late effects. This report provides recommendations for screening and management of pediatric and adult SCID patients treated with HCT.

Authors
Heimall, J; Buckley, RH; Puck, J; Fleisher, TA; Gennery, AR; Haddad, E; Neven, B; Slatter, M; Roderick, S; Baker, KS; Dietz, AC; Duncan, C; Griffith, LM; Notarangelo, L; Pulsipher, MA; Cowan, MJ
MLA Citation
Heimall, J, Buckley, RH, Puck, J, Fleisher, TA, Gennery, AR, Haddad, E, Neven, B, Slatter, M, Roderick, S, Baker, KS, Dietz, AC, Duncan, C, Griffith, LM, Notarangelo, L, Pulsipher, MA, and Cowan, MJ. "Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.8 (August 2017): 1229-1240. (Review)
PMID
28479164
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
8
Publish Date
2017
Start Page
1229
End Page
1240
DOI
10.1016/j.bbmt.2017.04.026

Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry.

We evaluated the overall and site-specific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the United States Immune Deficiency Network (USIDNET) registry compared with age-adjusted cancer incidence in the Surveillance, Epidemiology and End Results Program (SEER) database.We hypothesized that subjects with PIDD would have an increased incidence of cancer due to impaired immune function.Overall and site-specific cancer incidence rates were evaluated in subjects with PIDD (n = 3658) enrolled in the USIDNET registry from 2003 to 2015 and compared with age-adjusted incidence rates in the SEER database.We observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared with the age-adjusted SEER population (P < .001). Men with PIDD had a 1.91-fold excess relative risk of cancer compared with the age-adjusted male population (P < .001), while women with PIDD had similar overall cancer rates compared with the age-adjusted female population. Of the 4 most common malignancies in men and women in SEER (lung, colon, breast, and prostate cancers), we found no significant increase in these diagnoses in subjects with PIDD. Significant increases in lymphoma in both men (10-fold increase, P < .001) and women (8.34-fold increase, P < .001) with PIDD were observed.Excess incidence of cancer occurred in subjects with PIDD. An excess of lymphoma in specific PIDD populations principally drove this increased incidence, while no increased risk of the most common solid tumor malignancies was observed. These data point to a restricted role of the immune system in protecting from specific cancers.

Authors
Mayor, PC; Eng, KH; Singel, KL; Abrams, SI; Odunsi, K; Moysich, KB; Fuleihan, R; Garabedian, E; Lugar, P; Ochs, HD; Bonilla, FA; Buckley, RH; Sullivan, KE; Ballas, ZK; Cunningham-Rundles, C; Segal, BH
MLA Citation
Mayor, PC, Eng, KH, Singel, KL, Abrams, SI, Odunsi, K, Moysich, KB, Fuleihan, R, Garabedian, E, Lugar, P, Ochs, HD, Bonilla, FA, Buckley, RH, Sullivan, KE, Ballas, ZK, Cunningham-Rundles, C, and Segal, BH. "Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry." The Journal of allergy and clinical immunology (June 9, 2017).
PMID
28606585
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Publish Date
2017
DOI
10.1016/j.jaci.2017.05.024

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.

Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT).Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used.Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved.RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.

Authors
Slack, J; Albert, MH; Balashov, D; Belohradsky, BH; Bertaina, A; Bleesing, J; Booth, C; Buechner, J; Buckley, RH; Ouachée-Chardin, M; Deripapa, E; Drabko, K; Eapen, M; Feuchtinger, T; Finocchi, A; Gaspar, HB; Ghosh, S; Gillio, A; Gonzalez-Granado, LI; Grunebaum, E; Güngör, T; Heilmann, C; Helminen, M; Higuchi, K; Imai, K; Kalwak, K; Kanazawa, N; Karasu, G; Kucuk, ZY; Laberko, A; Lange, A; Mahlaoui, N; Meisel, R; Moshous, D; Muramatsu, H; Parikh, S; Pasic, S; Schmid, I; Schuetz, C; Schulz, A et al.
MLA Citation
Slack, J, Albert, MH, Balashov, D, Belohradsky, BH, Bertaina, A, Bleesing, J, Booth, C, Buechner, J, Buckley, RH, Ouachée-Chardin, M, Deripapa, E, Drabko, K, Eapen, M, Feuchtinger, T, Finocchi, A, Gaspar, HB, Ghosh, S, Gillio, A, Gonzalez-Granado, LI, Grunebaum, E, Güngör, T, Heilmann, C, Helminen, M, Higuchi, K, Imai, K, Kalwak, K, Kanazawa, N, Karasu, G, Kucuk, ZY, Laberko, A, Lange, A, Mahlaoui, N, Meisel, R, Moshous, D, Muramatsu, H, Parikh, S, Pasic, S, Schmid, I, Schuetz, C, and Schulz, A et al. "Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders." The Journal of allergy and clinical immunology (April 6, 2017).
Website
http://hdl.handle.net/10161/14232
PMID
28392333
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Publish Date
2017
DOI
10.1016/j.jaci.2017.02.036

Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT

Authors
Heimall, J; Puck, J; Buckley, R; Fleisher, TA; Gennery, AR; Neven, B; Slatter, M; Haddad, E; Notarangelo, LD; Baker, KS; Dietz, AC; Duncan, C; Pulsipher, MA; Cowan, MJ
MLA Citation
Heimall, J, Puck, J, Buckley, R, Fleisher, TA, Gennery, AR, Neven, B, Slatter, M, Haddad, E, Notarangelo, LD, Baker, KS, Dietz, AC, Duncan, C, Pulsipher, MA, and Cowan, MJ. "Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT." Biology of Blood and Marrow Transplantation 23.3 (March 2017): 379-387.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
3
Publish Date
2017
Start Page
379
End Page
387
DOI
10.1016/j.bbmt.2016.12.619

Clinical and imaging considerations in primary immunodeficiency disorders: an update.

Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders.

Authors
Wu, EY; Ehrlich, L; Handly, B; Frush, DP; Buckley, RH
MLA Citation
Wu, EY, Ehrlich, L, Handly, B, Frush, DP, and Buckley, RH. "Clinical and imaging considerations in primary immunodeficiency disorders: an update." Pediatric radiology 46.12 (November 2016): 1630-1644. (Review)
PMID
27655432
Source
epmc
Published In
Pediatric Radiology
Volume
46
Issue
12
Publish Date
2016
Start Page
1630
End Page
1644
DOI
10.1007/s00247-016-3684-x

Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids.

Authors
Sayour, EJ; Mousallem, T; Van Mater, D; Wang, E; Martin, P; Buckley, RH; Barfield, RC
MLA Citation
Sayour, EJ, Mousallem, T, Van Mater, D, Wang, E, Martin, P, Buckley, RH, and Barfield, RC. "Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia." Pediatric blood & cancer 63.10 (October 2016): 1856-1859.
PMID
27273469
Source
epmc
Published In
Pediatric Blood & Cancer
Volume
63
Issue
10
Publish Date
2016
Start Page
1856
End Page
1859
DOI
10.1002/pbc.26092

50 Years Ago in TheJournal ofPediatrics: Nutritional and Antigenic Effects of 2 Bovine Milk Preparations in Infants.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "50 Years Ago in TheJournal ofPediatrics: Nutritional and Antigenic Effects of 2 Bovine Milk Preparations in Infants." The Journal of pediatrics 175 (August 2016): 67-.
PMID
27507314
Source
epmc
Published In
The Journal of Pediatrics
Volume
175
Publish Date
2016
Start Page
67
DOI
10.1016/j.jpeds.2016.01.059

Hyper IgM Syndrome: a Report from the USIDNET Registry.

The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM).The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality.Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients' age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years).Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

Authors
Leven, EA; Maffucci, P; Ochs, HD; Scholl, PR; Buckley, RH; Fuleihan, RL; Geha, RS; Cunningham, CK; Bonilla, FA; Conley, ME; Ferdman, RM; Hernandez-Trujillo, V; Puck, JM; Sullivan, K; Secord, EA; Ramesh, M; Cunningham-Rundles, C
MLA Citation
Leven, EA, Maffucci, P, Ochs, HD, Scholl, PR, Buckley, RH, Fuleihan, RL, Geha, RS, Cunningham, CK, Bonilla, FA, Conley, ME, Ferdman, RM, Hernandez-Trujillo, V, Puck, JM, Sullivan, K, Secord, EA, Ramesh, M, and Cunningham-Rundles, C. "Hyper IgM Syndrome: a Report from the USIDNET Registry." July 2016.
PMID
27189378
Source
epmc
Published In
Journal of Clinical Immunology
Volume
36
Issue
5
Publish Date
2016
Start Page
490
End Page
501
DOI
10.1007/s10875-016-0291-4

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome.

Authors
Petrovski, S; Parrott, RE; Roberts, JL; Huang, H; Yang, J; Gorentla, B; Mousallem, T; Wang, E; Armstrong, M; McHale, D; MacIver, NJ; Goldstein, DB; Zhong, X-P; Buckley, RH
MLA Citation
Petrovski, S, Parrott, RE, Roberts, JL, Huang, H, Yang, J, Gorentla, B, Mousallem, T, Wang, E, Armstrong, M, McHale, D, MacIver, NJ, Goldstein, DB, Zhong, X-P, and Buckley, RH. "Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature." Journal of clinical immunology 36.5 (July 2016): 462-471.
Website
http://hdl.handle.net/10161/11947
PMID
27076228
Source
epmc
Published In
Journal of Clinical Immunology
Volume
36
Issue
5
Publish Date
2016
Start Page
462
End Page
471
DOI
10.1007/s10875-016-0281-6

Progress toward less toxic conditioning.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Progress toward less toxic conditioning." Blood 128.3 (July 2016): 322-323.
Website
http://hdl.handle.net/10161/12489
PMID
27445411
Source
epmc
Published In
Blood
Volume
128
Issue
3
Publish Date
2016
Start Page
322
End Page
323
DOI
10.1182/blood-2016-06-719922

Hyper IgM Syndrome: a Report from the USIDNET Registry

Authors
Leven, EA; Maffucci, P; Ochs, HD; Scholl, PR; Buckley, RH; Fuleihan, RL; Geha, RS; Cunningham, CK; Bonilla, FA; Conley, ME; Ferdman, RM; Hernandez-Trujillo, V; Puck, JM; Sullivan, K; Secord, EA; Ramesh, M; Cunningham-Rundles, C
MLA Citation
Leven, EA, Maffucci, P, Ochs, HD, Scholl, PR, Buckley, RH, Fuleihan, RL, Geha, RS, Cunningham, CK, Bonilla, FA, Conley, ME, Ferdman, RM, Hernandez-Trujillo, V, Puck, JM, Sullivan, K, Secord, EA, Ramesh, M, and Cunningham-Rundles, C. "Hyper IgM Syndrome: a Report from the USIDNET Registry." JOURNAL OF CLINICAL IMMUNOLOGY 36.5 (July 2016): 490-501.
Source
wos-lite
Published In
Journal of Clinical Immunology
Volume
36
Issue
5
Publish Date
2016
Start Page
490
End Page
501
DOI
10.1007/s10875-016-0291-4

Poor T Cell Reconstitution at 100 Days after T Cell-Replete Hematopoietic Cell Transplantation (HCT) for SCID Is Associated with Later Risk of Death or Need for 2nd Transplant in the 6901 Prospective Study of the Pidtc

Authors
Heimall, J; Logan, BR; Cowan, MJ; Notarangelo, LD; Puck, J; Fleisher, T; Griffith, LM; Kohn, DB; Pulsipher, MA; Shearer, W; Hanson, IC; Kapoor, N; O'Reilly, RJ; Boyer, M; Pai, S-Y; Parikh, S; Goldman, F; Burroughs, L; Marsh, RA; Kletzel, M; Thakar, M; Connelly, JA; Cuvellier, G; Loechelt, B; Shereck, E; Knudsen, A; Sullivan, K; DeSantes, K; Gillio, AP; Haddad, E; Petrovic, A; Quigg, TC; Smith, AR; Stenger, E; Dvorak, CC; Buckley, RH
MLA Citation
Heimall, J, Logan, BR, Cowan, MJ, Notarangelo, LD, Puck, J, Fleisher, T, Griffith, LM, Kohn, DB, Pulsipher, MA, Shearer, W, Hanson, IC, Kapoor, N, O'Reilly, RJ, Boyer, M, Pai, S-Y, Parikh, S, Goldman, F, Burroughs, L, Marsh, RA, Kletzel, M, Thakar, M, Connelly, JA, Cuvellier, G, Loechelt, B, Shereck, E, Knudsen, A, Sullivan, K, DeSantes, K, Gillio, AP, Haddad, E, Petrovic, A, Quigg, TC, Smith, AR, Stenger, E, Dvorak, CC, and Buckley, RH. "Poor T Cell Reconstitution at 100 Days after T Cell-Replete Hematopoietic Cell Transplantation (HCT) for SCID Is Associated with Later Risk of Death or Need for 2nd Transplant in the 6901 Prospective Study of the Pidtc." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S101
End Page
S102

Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.

X-linked hyper-IgM syndrome (X-HIGM) due to mutations in the gene encoding CD40 ligand results in failure of Ig class switching and an increased propensity for recurrent sinopulmonary and other infections, and thus decreased life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative, but long-term follow-up data are limited.We conducted a retrospective analysis of seven patients who have undergone allogeneic HSCT for HIGM syndrome at Duke University Medical Center.Median age at transplant was 5.2 years (range 0.7-19.3). None of the patients had active hepatic or pulmonary disease immediately prior to transplant, but all had a history of serious infections. Five patients received myeloablative conditioning, and two patients received reduced intensity conditioning. Graft sources included bone marrow, peripheral blood, and unrelated umbilical cord blood. Post-transplantation complications included veno-occlusive disease, hemorrhagic cystitis, adenoviremia, and cryptosporidium recurrence in one patient each. Two patients developed acute GVHD grades II-IV that resolved promptly with treatment and none developed extensive chronic GVHD. All patients are intravenous IgG-independent and 6/7 have normal antibody titers. Immunoglobulin (Ig) A levels normalized in all but one patient and T and B cell numbers and function are otherwise normal in all. All patients are alive at a median follow-up of 9.7 (range 9.7-16.1) years post-transplantation with predominantly donor chimerism and no recurrent infections.Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.

Authors
Allewelt, H; Martin, PL; Szabolcs, P; Chao, N; Buckley, R; Parikh, S
MLA Citation
Allewelt, H, Martin, PL, Szabolcs, P, Chao, N, Buckley, R, and Parikh, S. "Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience." Pediatric blood & cancer 62.12 (December 2015): 2216-2222.
PMID
26291959
Source
epmc
Published In
Pediatric Blood & Cancer
Volume
62
Issue
12
Publish Date
2015
Start Page
2216
End Page
2222
DOI
10.1002/pbc.25711

Combined immunodeficiency in the United States and Kuwait: Comparison of patients' characteristics and molecular diagnosis.

To compare different variables among (S)CID patients diagnosed in the USA and Kuwait.Review of patients registered in The US Immune Deficiency Network registry or Kuwait National PID Registry between 2004 and 2014.Totals of 98 and 69 (S)CID patients were registered during the study period in the USIDNET registry and the KNPIDR, respectively. The average annual incidence rate for the period 2004-2014 of (S)CID in children in Kuwait was 13.01/100,000 children, with an estimated occurrence of 1/7500 live births. There were differences between the two countries in the following variables: age at onset and diagnosis, family history of (S)CID, parental consanguinity, and outcome. More than 14% of (S)CID patients from USIDNET registry were diagnosed through newborn screening.Patients' characteristics and molecular causes of S(CID) are different between USA and Kuwait. NBS for SCID should be started in countries where the incidence of (S)CID is high.

Authors
Al-Herz, W; Notarangelo, LD; Sadek, A; Buckley, R; USIDNET Consortium,
MLA Citation
Al-Herz, W, Notarangelo, LD, Sadek, A, Buckley, R, and USIDNET Consortium, . "Combined immunodeficiency in the United States and Kuwait: Comparison of patients' characteristics and molecular diagnosis." Clinical immunology (Orlando, Fla.) 161.2 (December 2015): 170-173.
PMID
26248333
Source
epmc
Published In
Clinical Immunology
Volume
161
Issue
2
Publish Date
2015
Start Page
170
End Page
173
DOI
10.1016/j.clim.2015.07.013

Clinical application of whole-genome sequencing in patients with primary immunodeficiency.

Authors
Mousallem, T; Urban, TJ; McSweeney, KM; Kleinstein, SE; Zhu, M; Adeli, M; Parrott, RE; Roberts, JL; Krueger, B; Buckley, RH; Goldstein, DB
MLA Citation
Mousallem, T, Urban, TJ, McSweeney, KM, Kleinstein, SE, Zhu, M, Adeli, M, Parrott, RE, Roberts, JL, Krueger, B, Buckley, RH, and Goldstein, DB. "Clinical application of whole-genome sequencing in patients with primary immunodeficiency." The Journal of allergy and clinical immunology 136.2 (August 2015): 476-9.e6. (Letter)
PMID
25981738
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Volume
136
Issue
2
Publish Date
2015
Start Page
476
End Page
9.e6
DOI
10.1016/j.jaci.2015.02.040

Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC), and Absent Thymic Shadow: Diagnostic Clues for All Molecular Forms of Severe Combined Immunodeficiency (SCID).

Severe combined immunodeficiency (SCID) is a syndrome uniformly fatal during infancy unless recognized and treated successfully by bone marrow transplantation or gene therapy. Because infants with SCID have no abnormal physical appearance, diagnosis is usually delayed unless newborn screening is performed.In this study, we sought to evaluate the presenting features of all 172 patients with SCID transplanted at this institution over the past 31 years.We reviewed original charts from 172 consecutive patients with classic SCID who received either T-cell-depleted HLA-haploidentical (N = 154) or HLA-identical (N = 18) nonablative related marrow transplants at Duke University Medical Center from 1982 to 2013.The mean age at presentation was 4.87 months. When there was a family history of early infant death or known SCID (37%), the mean presentation age was much earlier, 2.0 months compared with 6.6 months. Failure to thrive was common, with 84 patients (50%) having a weight less than the 5th percentile. The leading infections included oral moniliasis (43%), viral infections (35.5%), and Pneumocystis jiroveci (26%) pneumonia. The group mean absolute lymphocyte count (ALC) was 1454/cmm; 88% of the infants had an ALC less than 3000/cmm. An absent thymic shadow was seen in 92% of infants with electronic radiographic data available. An absence of T-cell function was found in all patients.Infants with SCID appear normal at birth but later present with failure to thrive and/or recurrent fungal, viral, and bacterial infections. Low ALCs and an absent thymic shadow on chest x-ray are key diagnostic clues. The absence of T-cell function confirms the diagnosis.

Authors
McWilliams, LM; Dell Railey, M; Buckley, RH
MLA Citation
McWilliams, LM, Dell Railey, M, and Buckley, RH. "Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC), and Absent Thymic Shadow: Diagnostic Clues for All Molecular Forms of Severe Combined Immunodeficiency (SCID)." The journal of allergy and clinical immunology. In practice 3.4 (July 2015): 585-591.
PMID
25824440
Source
epmc
Published In
Journal of Allergy and Clinical Immunology: In Practice
Volume
3
Issue
4
Publish Date
2015
Start Page
585
End Page
591
DOI
10.1016/j.jaip.2015.01.026

Human DOCK2 mutations underlie an autosomal recessive pleiotropic immunodeficiency with early-onset invasive infections.

Authors
Buckley, RH; Dobbs, K
MLA Citation
Buckley, RH, and Dobbs, K. "Human DOCK2 mutations underlie an autosomal recessive pleiotropic immunodeficiency with early-onset invasive infections." The New England journal of medicine 372.25 (June 17, 2015): 2409-2422.
Website
http://hdl.handle.net/10161/10228
Source
manual
Published In
The New England journal of medicine
Volume
372
Issue
25
Publish Date
2015
Start Page
2409
End Page
2422

Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.).

Authors
Dobbs, K; Domínguez Conde, C; Zhang, S-Y; Parolini, S; Audry, M; Chou, J; Haapaniemi, E; Keles, S; Bilic, I; Okada, S; Massaad, MJ; Rounioja, S; Alwahadneh, AM; Serwas, NK; Capuder, K; Çiftçi, E; Felgentreff, K; Ohsumi, TK; Pedergnana, V; Boisson, B; Haskoloğlu, Ş; Ensari, A; Schuster, M; Moretta, A; Itan, Y; Patrizi, O; Rozenberg, F; Lebon, P; Saarela, J; Knip, M; Petrovski, S; Goldstein, DB; Parrott, RE; Savas, B; Schambach, A; Tabellini, G; Bock, C; Chatila, TA; Comeau, AM; Geha, RS; Abel, L et al.
MLA Citation
Dobbs, K, Domínguez Conde, C, Zhang, S-Y, Parolini, S, Audry, M, Chou, J, Haapaniemi, E, Keles, S, Bilic, I, Okada, S, Massaad, MJ, Rounioja, S, Alwahadneh, AM, Serwas, NK, Capuder, K, Çiftçi, E, Felgentreff, K, Ohsumi, TK, Pedergnana, V, Boisson, B, Haskoloğlu, Ş, Ensari, A, Schuster, M, Moretta, A, Itan, Y, Patrizi, O, Rozenberg, F, Lebon, P, Saarela, J, Knip, M, Petrovski, S, Goldstein, DB, Parrott, RE, Savas, B, Schambach, A, Tabellini, G, Bock, C, Chatila, TA, Comeau, AM, Geha, RS, and Abel, L et al. "Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections." The New England journal of medicine 372.25 (June 2015): 2409-2422.
PMID
26083206
Source
epmc
Published In
The New England journal of medicine
Volume
372
Issue
25
Publish Date
2015
Start Page
2409
End Page
2422
DOI
10.1056/nejmoa1413462

Successful treatment of disseminated BCG in a patient with severe combined immunodeficiency.

Authors
Smith, LL; Wright, BL; Buckley, RH
MLA Citation
Smith, LL, Wright, BL, and Buckley, RH. "Successful treatment of disseminated BCG in a patient with severe combined immunodeficiency." The journal of allergy and clinical immunology. In practice 3.3 (May 2015): 438-440. (Letter)
PMID
25609354
Source
epmc
Published In
Journal of Allergy and Clinical Immunology: In Practice
Volume
3
Issue
3
Publish Date
2015
Start Page
438
End Page
440
DOI
10.1016/j.jaip.2014.12.004

Tolerance and immunity after sequential lung and bone marrow transplantation from an unrelated cadaveric donor.

Authors
Szabolcs, P; Buckley, RH; Davis, RD; Moffet, J; Voynow, J; Antony, J; Chen, X; Sempowski, GD; Zaas, DW
MLA Citation
Szabolcs, P, Buckley, RH, Davis, RD, Moffet, J, Voynow, J, Antony, J, Chen, X, Sempowski, GD, and Zaas, DW. "Tolerance and immunity after sequential lung and bone marrow transplantation from an unrelated cadaveric donor." The Journal of allergy and clinical immunology 135.2 (February 2015): 567-570. (Letter)
PMID
25262460
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Volume
135
Issue
2
Publish Date
2015
Start Page
567
End Page
570
DOI
10.1016/j.jaci.2014.07.058

Early Hematopoietic Cell Transplant (HCT) Outcomes of Children with Severe Combined Immunodeficiency Disease (SCID): The First Seventy Four Patients of the Primary Immune Deficiency Treatment Consortium (PIDTC) Prospective Study 6901

Authors
Heimall, J; Logan, BR; Cowan, MJ; Notarangelo, LD; Griffith, LM; Puck, J; Parikh, S; O'Reilly, RJ; Pai, S-Y; Hanson, IC; Martinez, C; Pulsipher, MA; Kapoor, N; Goldman, F; Kletzel, M; Filipovich, L; Cuvellier, G; Thakar, M; Burroughs, L; Knudsen, A; Connelly, JA; Quigg, TC; Smith, AR; Sullivan, K; Loechelt, BJ; Gillio, AP; Haddad, E; Kohn, DB; Fleisher, T; Shearer, W; Dvorak, CC; Buckley, RH
MLA Citation
Heimall, J, Logan, BR, Cowan, MJ, Notarangelo, LD, Griffith, LM, Puck, J, Parikh, S, O'Reilly, RJ, Pai, S-Y, Hanson, IC, Martinez, C, Pulsipher, MA, Kapoor, N, Goldman, F, Kletzel, M, Filipovich, L, Cuvellier, G, Thakar, M, Burroughs, L, Knudsen, A, Connelly, JA, Quigg, TC, Smith, AR, Sullivan, K, Loechelt, BJ, Gillio, AP, Haddad, E, Kohn, DB, Fleisher, T, Shearer, W, Dvorak, CC, and Buckley, RH. "Early Hematopoietic Cell Transplant (HCT) Outcomes of Children with Severe Combined Immunodeficiency Disease (SCID): The First Seventy Four Patients of the Primary Immune Deficiency Treatment Consortium (PIDTC) Prospective Study 6901." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S289
End Page
S291

Positive family history, infection, low absolute lymphocyte count (ALC), and absent thymic shadow: Diagnostic clues for all molecular forms of severe combined immunodeficiency (SCID)

© 2015 American Academy of Allergy, Asthma & Immunology. BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome uniformly fatal during infancy unless recognized and treated successfully by bone marrow transplantation or gene therapy. Because infants with SCID have no abnormal physical appearance, diagnosis is usually delayed unless newborn screening is performed. OBJECTIVE: In this study, we sought to evaluate the presenting features of all 172 patients with SCID transplanted at this institution over the past 31 years. METHODS: We reviewed original charts from 172 consecutive patients with classic SCID who received either T-cell-depleted HLA-haploidentical (N = 154) or HLA-identical (N = 18) nonablative related marrow transplants at Duke University Medical Center from 1982 to 2013. RESULTS: The mean age at presentation was 4.87 months. When there was a family history of early infant death or known SCID (37%), the mean presentation age was much earlier, 2.0 months compared with 6.6 months. Failure to thrive was common, with 84 patients (50%) having a weight less than the 5th percentile. The leading infections included oral moniliasis (43%), viral infections (35.5%), and Pneumocystis jiroveci (26%) pneumonia. The group mean absolute lymphocyte count (ALC) was 1454/cmm; 88% of the infants had an ALC less than 3000/cmm. An absent thymic shadow was seen in 92% of infants with electronic radiographic data available. An absence of T-cell function was found in all patients. CONCLUSIONS: Infants with SCID appear normal at birth but later present with failure to thrive and/or recurrent fungal, viral, and bacterial infections. Low ALCs and an absent thymic shadow on chest x-ray are key diagnostic clues. The absence of T-cell function confirms the diagnosis.

Authors
McWilliams, LM; Railey, MD; Buckley, RH
MLA Citation
McWilliams, LM, Railey, MD, and Buckley, RH. "Positive family history, infection, low absolute lymphocyte count (ALC), and absent thymic shadow: Diagnostic clues for all molecular forms of severe combined immunodeficiency (SCID)." Journal of Allergy and Clinical Immunology: In Practice 3.4 (January 1, 2015): 585-591.
Source
scopus
Published In
Journal of Allergy and Clinical Immunology: In Practice
Volume
3
Issue
4
Publish Date
2015
Start Page
585
End Page
591
DOI
10.1016/j.jaip.2015.01.026

American Pediatric Society's 2014 John Howland Award acceptance lecture: saving lives through early diagnosis.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "American Pediatric Society's 2014 John Howland Award acceptance lecture: saving lives through early diagnosis." Pediatric research 76.5 (November 2014): 491-494.
PMID
25211637
Source
epmc
Published In
Pediatric Research
Volume
76
Issue
5
Publish Date
2014
Start Page
491
End Page
494
DOI
10.1038/pr.2014.123

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency.

Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy.We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs.We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66).Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001).Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.

Authors
Dvorak, CC; Hassan, A; Slatter, MA; Hönig, M; Lankester, AC; Buckley, RH; Pulsipher, MA; Davis, JH; Güngör, T; Gabriel, M; Bleesing, JH; Bunin, N; Sedlacek, P; Connelly, JA; Crawford, DF; Notarangelo, LD; Pai, S-Y; Hassid, J; Veys, P; Gennery, AR; Cowan, MJ
MLA Citation
Dvorak, CC, Hassan, A, Slatter, MA, Hönig, M, Lankester, AC, Buckley, RH, Pulsipher, MA, Davis, JH, Güngör, T, Gabriel, M, Bleesing, JH, Bunin, N, Sedlacek, P, Connelly, JA, Crawford, DF, Notarangelo, LD, Pai, S-Y, Hassid, J, Veys, P, Gennery, AR, and Cowan, MJ. "Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency." The Journal of allergy and clinical immunology 134.4 (October 2014): 935-943.e15.
PMID
25109802
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Volume
134
Issue
4
Publish Date
2014
Start Page
935
End Page
943.e15
DOI
10.1016/j.jaci.2014.06.021

A nonsense mutation in IKBKB causes combined immunodeficiency.

Identification of the molecular etiologies of primary immunodeficiencies has led to important insights into the development and function of the immune system. We report here the cause of combined immunodeficiency in 4 patients from 2 different consanguineous Qatari families with similar clinical and immunologic phenotypes. The patients presented at an early age with fungal, viral, and bacterial infections and hypogammaglobulinemia. Although their B- and T-cell numbers were normal, they had low regulatory T-cell and NK-cell numbers. Moreover, patients' T cells were mostly CD45RA(+)-naive cells and were defective in activation after T-cell receptor stimulation. All patients contained the same homozygous nonsense mutation in IKBKB (R286X), revealed by whole-exome sequencing with undetectable IKKβ and severely decreased NEMO proteins. Mutant IKKβ(R286X) was unable to complex with IKKα/NEMO. Immortalized patient B cells displayed impaired IκBα phosphorylation and NFκB nuclear translocation. These data indicate that mutated IKBKB is the likely cause of immunodeficiency in these 4 patients.

Authors
Mousallem, T; Yang, J; Urban, TJ; Wang, H; Adeli, M; Parrott, RE; Roberts, JL; Goldstein, DB; Buckley, RH; Zhong, X-P
MLA Citation
Mousallem, T, Yang, J, Urban, TJ, Wang, H, Adeli, M, Parrott, RE, Roberts, JL, Goldstein, DB, Buckley, RH, and Zhong, X-P. "A nonsense mutation in IKBKB causes combined immunodeficiency." Blood 124.13 (September 2014): 2046-2050.
PMID
25139357
Source
epmc
Published In
Blood
Volume
124
Issue
13
Publish Date
2014
Start Page
2046
End Page
2050
DOI
10.1182/blood-2014-04-571265

Diagnostic Immunization with Bacteriophage ΦX 174 in Patients with Common Variable Immunodeficiency/Hypogammaglobulinemia

Authors
Smith, LL; Buckley, R; Lugar, P
MLA Citation
Smith, LL, Buckley, R, and Lugar, P. "Diagnostic Immunization with Bacteriophage ΦX 174 in Patients with Common Variable Immunodeficiency/Hypogammaglobulinemia." Frontiers in Immunology 5 (August 29, 2014).
Source
crossref
Published In
Frontiers in Immunology
Volume
5
Publish Date
2014
DOI
10.3389/fimmu.2014.00410

Transplantation outcomes for severe combined immunodeficiency, 2000-2009.

The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth.We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009).Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell-depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival.Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Authors
Pai, S-Y; Logan, BR; Griffith, LM; Buckley, RH; Parrott, RE; Dvorak, CC; Kapoor, N; Hanson, IC; Filipovich, AH; Jyonouchi, S; Sullivan, KE; Small, TN; Burroughs, L; Skoda-Smith, S; Haight, AE; Grizzle, A; Pulsipher, MA; Chan, KW; Fuleihan, RL; Haddad, E; Loechelt, B; Aquino, VM; Gillio, A; Davis, J; Knutsen, A; Smith, AR; Moore, TB; Schroeder, ML; Goldman, FD; Connelly, JA; Porteus, MH; Xiang, Q; Shearer, WT; Fleisher, TA; Kohn, DB; Puck, JM; Notarangelo, LD; Cowan, MJ; O'Reilly, RJ
MLA Citation
Pai, S-Y, Logan, BR, Griffith, LM, Buckley, RH, Parrott, RE, Dvorak, CC, Kapoor, N, Hanson, IC, Filipovich, AH, Jyonouchi, S, Sullivan, KE, Small, TN, Burroughs, L, Skoda-Smith, S, Haight, AE, Grizzle, A, Pulsipher, MA, Chan, KW, Fuleihan, RL, Haddad, E, Loechelt, B, Aquino, VM, Gillio, A, Davis, J, Knutsen, A, Smith, AR, Moore, TB, Schroeder, ML, Goldman, FD, Connelly, JA, Porteus, MH, Xiang, Q, Shearer, WT, Fleisher, TA, Kohn, DB, Puck, JM, Notarangelo, LD, Cowan, MJ, and O'Reilly, RJ. "Transplantation outcomes for severe combined immunodeficiency, 2000-2009." The New England journal of medicine 371.5 (July 2014): 434-446.
PMID
25075835
Source
epmc
Published In
The New England journal of medicine
Volume
371
Issue
5
Publish Date
2014
Start Page
434
End Page
446
DOI
10.1056/nejmoa1401177

Actionable diagnosis of neuroleptospirosis by next-generation sequencing.

A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.

Authors
Wilson, MR; Naccache, SN; Samayoa, E; Biagtan, M; Bashir, H; Yu, G; Salamat, SM; Somasekar, S; Federman, S; Miller, S; Sokolic, R; Garabedian, E; Candotti, F; Buckley, RH; Reed, KD; Meyer, TL; Seroogy, CM; Galloway, R; Henderson, SL; Gern, JE; DeRisi, JL; Chiu, CY
MLA Citation
Wilson, MR, Naccache, SN, Samayoa, E, Biagtan, M, Bashir, H, Yu, G, Salamat, SM, Somasekar, S, Federman, S, Miller, S, Sokolic, R, Garabedian, E, Candotti, F, Buckley, RH, Reed, KD, Meyer, TL, Seroogy, CM, Galloway, R, Henderson, SL, Gern, JE, DeRisi, JL, and Chiu, CY. "Actionable diagnosis of neuroleptospirosis by next-generation sequencing." The New England journal of medicine 370.25 (June 4, 2014): 2408-2417.
PMID
24896819
Source
epmc
Published In
The New England journal of medicine
Volume
370
Issue
25
Publish Date
2014
Start Page
2408
End Page
2417
DOI
10.1056/nejmoa1401268

Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts.

The present uncertainty of which live viral or bacterial vaccines can be given to immunodeficient patients and the growing neglect of societal adherence to routine immunizations has prompted the Medical Advisory Committee of the Immune Deficiency Foundation to issue recommendations based on published literature and the collective experience of the committee members. These recommendations address the concern for immunodeficient patients acquiring infections from healthy subjects who have not been immunized or who are shedding live vaccine-derived viral or bacterial organisms. Such transmission of infectious agents can occur within the hospital, clinic, or home or at any public gathering. Collectively, we define this type of transmission as close-contact spread of infectious disease that is particularly relevant in patients with impaired immunity who might have an infection when exposed to subjects carrying vaccine-preventable infectious diseases or who have recently received a live vaccine. Immunodeficient patients who have received therapeutic hematopoietic stem transplantation are also at risk during the time when immune reconstitution is incomplete or while they are receiving immunosuppressive agents to prevent or treat graft-versus-host disease. This review recommends the general education of what is known about vaccine-preventable or vaccine-derived diseases being spread to immunodeficient patients at risk for close-contact spread of infection and describes the relative risks for a child with severe immunodeficiency. The review also recommends a balance between the need to protect vulnerable subjects and their social needs to integrate into society, attend school, and benefit from peer education.

Authors
Medical Advisory Committee of the Immune Deficiency Foundation, ; Shearer, WT; Fleisher, TA; Buckley, RH; Ballas, Z; Ballow, M; Blaese, RM; Bonilla, FA; Conley, ME; Cunningham-Rundles, C; Filipovich, AH; Fuleihan, R; Gelfand, EW; Hernandez-Trujillo, V; Holland, SM; Hong, R; Lederman, HM; Malech, HL; Miles, S; Notarangelo, LD; Ochs, HD; Orange, JS; Puck, JM; Routes, JM; Stiehm, ER; Sullivan, K; Torgerson, T; Winkelstein, J
MLA Citation
Medical Advisory Committee of the Immune Deficiency Foundation, , Shearer, WT, Fleisher, TA, Buckley, RH, Ballas, Z, Ballow, M, Blaese, RM, Bonilla, FA, Conley, ME, Cunningham-Rundles, C, Filipovich, AH, Fuleihan, R, Gelfand, EW, Hernandez-Trujillo, V, Holland, SM, Hong, R, Lederman, HM, Malech, HL, Miles, S, Notarangelo, LD, Ochs, HD, Orange, JS, Puck, JM, Routes, JM, Stiehm, ER, Sullivan, K, Torgerson, T, and Winkelstein, J. "Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts." The Journal of allergy and clinical immunology 133.4 (April 2014): 961-966. (Review)
PMID
24582311
Source
epmc
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
4
Publish Date
2014
Start Page
961
End Page
966
DOI
10.1016/j.jaci.2013.11.043

Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts

Authors
Shearer, WT; Fleisher, TA; Buckley, RH; Ballas, Z; Ballow, M; Blaese, RM; Bonilla, FA; Conley, ME; Cunningham-Rundles, C; Filipovich, AH; Fuleihan, R; Gelfand, EW; Hernandez-Trujillo, V; Holland, SM; Hong, R; Lederman, HM; Malech, HL; Miles, S; Notarangelo, LD; Ochs, HD; Orange, JS; Puck, JM; Routes, JM; Stiehm, ER; Sullivan, K; Torgerson, T; Winkelstein, J
MLA Citation
Shearer, WT, Fleisher, TA, Buckley, RH, Ballas, Z, Ballow, M, Blaese, RM, Bonilla, FA, Conley, ME, Cunningham-Rundles, C, Filipovich, AH, Fuleihan, R, Gelfand, EW, Hernandez-Trujillo, V, Holland, SM, Hong, R, Lederman, HM, Malech, HL, Miles, S, Notarangelo, LD, Ochs, HD, Orange, JS, Puck, JM, Routes, JM, Stiehm, ER, Sullivan, K, Torgerson, T, and Winkelstein, J. "Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts." Journal of Allergy and Clinical Immunology 133.4 (April 2014): 961-966.
Source
crossref
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
4
Publish Date
2014
Start Page
961
End Page
966
DOI
10.1016/j.jaci.2013.11.043

Dna Ligase IV Deficiency With Novel Compound Heterozygous Mutations

Authors
Caldwell, JW; Mousallem, TI; Dixon, N; Buckley, RH; Parikh, SH
MLA Citation
Caldwell, JW, Mousallem, TI, Dixon, N, Buckley, RH, and Parikh, SH. "Dna Ligase IV Deficiency With Novel Compound Heterozygous Mutations." April 2014.
Source
wos-lite
Published In
Journal of Clinical Immunology
Volume
34
Issue
3
Publish Date
2014
Start Page
391
End Page
391

Primary Immune Deficiency Treatment Consortium (PIDTC) report

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives. © 2013 American Academy of Allergy, Asthma & Immunology.

Authors
Griffith, LM; Cowan, MJ; Notarangelo, LD; Kohn, DB; Puck, JM; Pai, SY; Ballard, B; Bauer, SC; Bleesing, JJH; Boyle, M; Brower, A; Buckley, RH; Van Der Burg, M; Burroughs, LM; Candotti, F; Cant, AJ; Chatila, T; Cunningham-Rundles, C; Dinauer, MC; Dvorak, CC; Filipovich, AH; Fleisher, TA; Bobby Gaspar, H; Gungor, T; Haddad, E; Hovermale, E; Huang, F; Hurley, A; Hurley, M; Iyengar, S; Kang, EM; Logan, BR; Long-Boyle, JR; Malech, HL; McGhee, SA; Modell, F; Modell, V; Ochs, HD; O'Reilly, RJ et al.
MLA Citation
Griffith, LM, Cowan, MJ, Notarangelo, LD, Kohn, DB, Puck, JM, Pai, SY, Ballard, B, Bauer, SC, Bleesing, JJH, Boyle, M, Brower, A, Buckley, RH, Van Der Burg, M, Burroughs, LM, Candotti, F, Cant, AJ, Chatila, T, Cunningham-Rundles, C, Dinauer, MC, Dvorak, CC, Filipovich, AH, Fleisher, TA, Bobby Gaspar, H, Gungor, T, Haddad, E, Hovermale, E, Huang, F, Hurley, A, Hurley, M, Iyengar, S, Kang, EM, Logan, BR, Long-Boyle, JR, Malech, HL, McGhee, SA, Modell, F, Modell, V, Ochs, HD, and O'Reilly, RJ et al. "Primary Immune Deficiency Treatment Consortium (PIDTC) report." Journal of Allergy and Clinical Immunology 133.2 (February 1, 2014). (Review)
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
2
Publish Date
2014
DOI
10.1016/j.jaci.2013.07.052

Whole-Exome Sequencing Reveals IKBKB As a Cause of Combined Immunodeficiency

Authors
Mousallem, T; Yang, J; Urban, TJ; Wang, H; Parrott, RE; Roberts, JL; Buckley, RH; Zhong, X; Goldstein, DB
MLA Citation
Mousallem, T, Yang, J, Urban, TJ, Wang, H, Parrott, RE, Roberts, JL, Buckley, RH, Zhong, X, and Goldstein, DB. "Whole-Exome Sequencing Reveals IKBKB As a Cause of Combined Immunodeficiency." February 2014.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
2
Publish Date
2014
Start Page
AB399
End Page
AB399

Diagnostic Immunization With Bacteriophage Phi X 174 In Patients With Common Variable Immunodeficiency/Hypogammaglobulinemia

Authors
Smith, L; Buckley, RH; Lugar, PL
MLA Citation
Smith, L, Buckley, RH, and Lugar, PL. "Diagnostic Immunization With Bacteriophage Phi X 174 In Patients With Common Variable Immunodeficiency/Hypogammaglobulinemia." February 2014.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
2
Publish Date
2014
Start Page
AB69
End Page
AB69

Retrospective Study of 240 Patients with Severe Combined Immunodeficiency Transplanted from 2000-2009: A Report from the Primary Immune Deficiency Treatment Consortium of North America

Authors
Pai, S-Y; Logan, BR; Griffith, LM; Buckley, RH; Parrott, RE; Dvorak, CC; Kapoor, N; Hanson, IC; Filipovich, A; Jyonouchi, S; Small, T; Burroughs, L; Haight, AE; Pulsipher, MA; Chan, KW; Fuleihan, R; Haddad, E; Loechelt, B; Aquino, V; Gillio, AP; Davis, JH; Knutsen, A; Smith, A; Moore, TB; Schroeder, M; Goldman, F; Connelly, JA; Porteus, MH; Xiang, Q; Shearer, W; Fleisher, T; Kohn, DB; Puck, J; Notarangelo, LD; Cowan, MJ; O'Reilly, R
MLA Citation
Pai, S-Y, Logan, BR, Griffith, LM, Buckley, RH, Parrott, RE, Dvorak, CC, Kapoor, N, Hanson, IC, Filipovich, A, Jyonouchi, S, Small, T, Burroughs, L, Haight, AE, Pulsipher, MA, Chan, KW, Fuleihan, R, Haddad, E, Loechelt, B, Aquino, V, Gillio, AP, Davis, JH, Knutsen, A, Smith, A, Moore, TB, Schroeder, M, Goldman, F, Connelly, JA, Porteus, MH, Xiang, Q, Shearer, W, Fleisher, T, Kohn, DB, Puck, J, Notarangelo, LD, Cowan, MJ, and O'Reilly, R. "Retrospective Study of 240 Patients with Severe Combined Immunodeficiency Transplanted from 2000-2009: A Report from the Primary Immune Deficiency Treatment Consortium of North America." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S24
End Page
S25

Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience

Background The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries. Objectives The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America. Methods Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group. Results Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%). Conclusion Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis. © 2013 American Academy of Allergy, Asthma & Immunology.

Authors
Shearer, WT; Dunn, E; Notarangelo, LD; Dvorak, CC; Puck, JM; Logan, BR; Griffith, LM; Kohn, DB; O'Reilly, RJ; Fleisher, TA; Pai, SY; Martinez, CA; Buckley, RH; Cowan, MJ
MLA Citation
Shearer, WT, Dunn, E, Notarangelo, LD, Dvorak, CC, Puck, JM, Logan, BR, Griffith, LM, Kohn, DB, O'Reilly, RJ, Fleisher, TA, Pai, SY, Martinez, CA, Buckley, RH, and Cowan, MJ. "Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience." Journal of Allergy and Clinical Immunology 133.4 (January 1, 2014): 1092-1098.
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Volume
133
Issue
4
Publish Date
2014
Start Page
1092
End Page
1098
DOI
10.1016/j.jaci.2013.09.044

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency

© 2014 American Academy of Allergy, Asthma and Immunology. Background Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. Objective We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. Methods We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66) Results Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). Conclusion Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.

Authors
Dvorak, CC; Hassan, A; Slatter, MA; Hönig, M; Lankester, AC; Buckley, RH; Pulsipher, MA; Davis, JH; Güngör, T; Gabriel, M; Bleesing, JH; Bunin, N; Sedlacek, P; Connelly, JA; Crawford, DF; Notarangelo, LD; Pai, SY; Hassid, J; Veys, P; Gennery, AR; Cowan, MJ
MLA Citation
Dvorak, CC, Hassan, A, Slatter, MA, Hönig, M, Lankester, AC, Buckley, RH, Pulsipher, MA, Davis, JH, Güngör, T, Gabriel, M, Bleesing, JH, Bunin, N, Sedlacek, P, Connelly, JA, Crawford, DF, Notarangelo, LD, Pai, SY, Hassid, J, Veys, P, Gennery, AR, and Cowan, MJ. "Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency." Journal of Allergy and Clinical Immunology 134.4 (January 1, 2014): 935-943.e15.
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Volume
134
Issue
4
Publish Date
2014
Start Page
935
End Page
943.e15
DOI
10.1016/j.jaci.2014.06.021

Primary Immunodeficiency Diseases

Authors
Buckley, RH; Orange, JS
MLA Citation
Buckley, RH, and Orange, JS. "Primary Immunodeficiency Diseases." Middleton's Allergy: Principles and Practice: Eighth Edition. October 18, 2013. 1144-1174.
Source
scopus
Volume
2-2
Publish Date
2013
Start Page
1144
End Page
1174
DOI
10.1016/B978-0-323-08593-9.00073-5

Long-term outcome of non-ablative booster BMT in patients with SCID.

SCID is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T cells. Immune reconstitution can be achieved through nonablative related donor BMT. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7% of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long-term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63%) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, P=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T-and B-cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Nonablative booster BMT can be lifesaving for SCID.

Authors
Teigland, CL; Parrott, RE; Buckley, RH
MLA Citation
Teigland, CL, Parrott, RE, and Buckley, RH. "Long-term outcome of non-ablative booster BMT in patients with SCID." Bone Marrow Transplant 48.8 (August 2013): 1050-1055.
Website
http://hdl.handle.net/10161/13739
PMID
23396406
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
48
Issue
8
Publish Date
2013
Start Page
1050
End Page
1055
DOI
10.1038/bmt.2013.6

RESPONSE TO BACTERIOPHAGE Phi chi 174 IN CHILDREN WITH PARTIAL DIGEORGE ANOMALY AND IN CHILDREN WITH COMPLETE DIGEORGE ANOMALY AFTER CULTURED POSTNATAL ALLOGENEIC THYMUS TRANSPLANTATION

Authors
Markert, ML; Gupton, SE; McCarthy, EA; Devlin, BH; Hsieh, C-S; Li, J; Torgerson, TR; Ochs, HD; Buckley, RH
MLA Citation
Markert, ML, Gupton, SE, McCarthy, EA, Devlin, BH, Hsieh, C-S, Li, J, Torgerson, TR, Ochs, HD, and Buckley, RH. "RESPONSE TO BACTERIOPHAGE Phi chi 174 IN CHILDREN WITH PARTIAL DIGEORGE ANOMALY AND IN CHILDREN WITH COMPLETE DIGEORGE ANOMALY AFTER CULTURED POSTNATAL ALLOGENEIC THYMUS TRANSPLANTATION." JOURNAL OF CLINICAL IMMUNOLOGY 33.3 (April 2013): 679-680.
Source
wos-lite
Published In
Journal of Clinical Immunology
Volume
33
Issue
3
Publish Date
2013
Start Page
679
End Page
680

Next Generation Sequencing May Be More Efficient and Economical Than Targeted Gene Testing in Patients with Primary Immune Deficiency (PID)

Authors
Mousallem, T; Urban, TJ; Roberts, JL; Parrott, RE; Goldstein, DB; Buckley, RH
MLA Citation
Mousallem, T, Urban, TJ, Roberts, JL, Parrott, RE, Goldstein, DB, and Buckley, RH. "Next Generation Sequencing May Be More Efficient and Economical Than Targeted Gene Testing in Patients with Primary Immune Deficiency (PID)." February 2013.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
131
Issue
2
Publish Date
2013
Start Page
AB52
End Page
AB52

Post-transplantation B cell function in different molecular types of SCID.

PURPOSE: Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of long-term survival. However, the development of B cell function has been more problematic. We report here results of analyses of B cell function in 125 SCID recipients prior to and long-term after non-ablative BMT, according to their molecular type. METHODS: Studies included blood immunoglobulin measurements; antibody titers to standard vaccines, blood group antigens and bacteriophage Φ X 174; flow cytometry to examine for markers of immaturity, memory, switched memory B cells and BAFF receptor expression; B cell chimerism; B cell spectratyping; and B cell proliferation. RESULTS: The results showed that B cell chimerism was not required for normal B cell function in IL7Rα-Def, ADA-Def and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J recombination defects, donor B cell chimerism was necessary for B cell function to develop. CONCLUSION: The most important factor determining whether B cell function develops in SCID T cell chimeras is the underlying molecular defect. In some types, host B cells function normally. In those molecular types where host B cell function did not develop, donor B cell chimerism was necessary to achieve B cell function. 236 words.

Authors
Buckley, RH; Win, CM; Moser, BK; Parrott, RE; Sajaroff, E; Sarzotti-Kelsoe, M
MLA Citation
Buckley, RH, Win, CM, Moser, BK, Parrott, RE, Sajaroff, E, and Sarzotti-Kelsoe, M. "Post-transplantation B cell function in different molecular types of SCID." J Clin Immunol 33.1 (January 2013): 96-110.
PMID
23001410
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
33
Issue
1
Publish Date
2013
Start Page
96
End Page
110
DOI
10.1007/s10875-012-9797-6

Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience

Authors
Shearer, WT; Dunn, E; Notarangelo, LD; Dvorak, CC; Puck, JM; Logan, BR; Griffith, LM; Kohn, DB; O'Reilly, RJ; Fleisher, TA; Pai, S-Y; Martinez, CA; Buckley, RH; Cowan, MJ
MLA Citation
Shearer, WT, Dunn, E, Notarangelo, LD, Dvorak, CC, Puck, JM, Logan, BR, Griffith, LM, Kohn, DB, O'Reilly, RJ, Fleisher, TA, Pai, S-Y, Martinez, CA, Buckley, RH, and Cowan, MJ. "Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience." Journal of Allergy and Clinical Immunology (2013).
PMID
24290292
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Publish Date
2013

The natural history of children with severe combined immunodeficiency: Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901

The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. © 2013 Springer Science+Business Media New York.

Authors
Dvorak, CC; Cowan, MJ; Logan, BR; Notarangelo, LD; Griffith, LM; Puck, JM; Kohn, DB; Shearer, WT; O'Reilly, RJ; Fleisher, TA; Pai, S-Y; Hanson, IC; Pulsipher, MA; Fuleihan, R; Filipovich, A; Goldman, F; Kapoor, N; Small, T; Smith, A; Chan, K-W; Cuvelier, G; Heimall, J; Knutsen, A; Loechelt, B; Moore, T; Buckley, RH
MLA Citation
Dvorak, CC, Cowan, MJ, Logan, BR, Notarangelo, LD, Griffith, LM, Puck, JM, Kohn, DB, Shearer, WT, O'Reilly, RJ, Fleisher, TA, Pai, S-Y, Hanson, IC, Pulsipher, MA, Fuleihan, R, Filipovich, A, Goldman, F, Kapoor, N, Small, T, Smith, A, Chan, K-W, Cuvelier, G, Heimall, J, Knutsen, A, Loechelt, B, Moore, T, and Buckley, RH. "The natural history of children with severe combined immunodeficiency: Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901." Journal of Clinical Immunology 33.7 (2013): 1156-1164.
Source
scival
Published In
Journal of Clinical Immunology
Volume
33
Issue
7
Publish Date
2013
Start Page
1156
End Page
1164
DOI
10.1007/s10875-013-9917-y

B-cell reconstitution for SCID: Should a conditioning regimen be used in SCID treatment?

Bone marrow transplantation has resulted in life-saving sustained T-cell reconstitution in many infants with severe combined immunodeficiency (SCID), but correction of B-cell function has been more problematic. At the annual meeting of the Primary Immunodeficiency Treatment Consortium held in Boston, Massachusetts, on April 27, 2012, a debate was held regarding the use of pretransplantation conditioning versus no pretransplantation conditioning in an effort to address this problem. Reviews of the literature were made by both debaters, and there was agreement that there was a higher rate of B-cell chimerism and a lower number of patients who required ongoing immunoglobulin replacement therapy in centers that used pretransplantation conditioning. However, there were still patients who required immunoglobulin replacement in those centers, and therefore pretransplantation conditioning did not guarantee development of B-cell function. Dr Rebecca H. Buckley presented data on B-cell function according to the molecular defect of the patient, and showed that patients with IL-7 receptor α, ADA, and CD3 chain gene mutations can have normal B-cell function after transplantation with only host B cells. Dr Elie Haddad presented a statistical analysis of B-cell function in published reports and showed that only a conditioning regimen that contained busulfan was significantly associated with better B-cell function after transplantation. The question is whether the risk of immediate and long-term toxicity with use of busulfan is justified, particularly in patients with SCID with DNA repair defects and in very young newborns with SCID who will be detected by using newborn screening. © 2013 American Academy of Allergy, Asthma & Immunology.

Authors
Haddad, E; Leroy, S; Buckley, RH
MLA Citation
Haddad, E, Leroy, S, and Buckley, RH. "B-cell reconstitution for SCID: Should a conditioning regimen be used in SCID treatment?." Journal of Allergy and Clinical Immunology (2013).
PMID
23465660
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Publish Date
2013
DOI
10.1016/j.jaci.2013.01.047

B-cell reconstitution for SCID: Should a conditioning regimen be used in SCID treatment?

Bone marrow transplantation has resulted in life-saving sustained T-cell reconstitution in many infants with severe combined immunodeficiency (SCID), but correction of B-cell function has been more problematic. At the annual meeting of the Primary Immunodeficiency Treatment Consortium held in Boston, Massachusetts, on April 27, 2012, a debate was held regarding the use of pretransplantation conditioning versus no pretransplantation conditioning in an effort to address this problem. Reviews of the literature were made by both debaters, and there was agreement that there was a higher rate of B-cell chimerism and a lower number of patients who required ongoing immunoglobulin replacement therapy in centers that used pretransplantation conditioning. However, there were still patients who required immunoglobulin replacement in those centers, and therefore pretransplantation conditioning did not guarantee development of B-cell function. Dr Rebecca H. Buckley presented data on B-cell function according to the molecular defect of the patient, and showed that patients with IL-7 receptor α, ADA, and CD3 chain gene mutations can have normal B-cell function after transplantation with only host B cells. Dr Elie Haddad presented a statistical analysis of B-cell function in published reports and showed that only a conditioning regimen that contained busulfan was significantly associated with better B-cell function after transplantation. The question is whether the risk of immediate and long-term toxicity with use of busulfan is justified, particularly in patients with SCID with DNA repair defects and in very young newborns with SCID who will be detected by using newborn screening. © 2013 American Academy of Allergy, Asthma & Immunology.

Authors
Haddad, E; Leroy, S; Buckley, RH
MLA Citation
Haddad, E, Leroy, S, and Buckley, RH. "B-cell reconstitution for SCID: Should a conditioning regimen be used in SCID treatment?." Journal of Allergy and Clinical Immunology 131.4 (2013): 994-1000.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
131
Issue
4
Publish Date
2013
Start Page
994
End Page
1000
DOI
10.1016/j.jaci.2013.01.047

Post-transplantation B cell function in different molecular types of SCID

Purpose Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of longterm survival. However, the development of B cell function has been more problematic. We report here results of analyses of B cell function in 125 SCID recipients prior to and long-term after non-ablative BMT, according to their molecular type. Methods Studies included blood immunoglobulin measurements; antibody titers to standard vaccines, blood group antigens and bacteriophage F X 174; flow cytometry to examine for markers of immaturity, memory, switched memory B cells and BAFF receptor expression; B cell chimerism; B cell spectratyping; and B cell proliferation. Results The results showed that B cell chimerism was not required for normal B cell function in IL7Ra-Def, ADADef and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J recombination defects, donor B cell chimerism was necessary for B cell function to develop. Conclusion The most important factor determining whether B cell function develops in SCID T cell chimeras is the underlying molecular defect. In some types, host B cells function normally. In those molecular types where host B cell function did not develop, donor B cell chimerism was necessary to achieve B cell function. 236 words. © Springer Science+Business Media, LLC 2012.

Authors
Buckley, RH; Win, CM; Moser, BK; Parrott, RE; Sajaroff, E; Sarzotti-Kelsoe, M
MLA Citation
Buckley, RH, Win, CM, Moser, BK, Parrott, RE, Sajaroff, E, and Sarzotti-Kelsoe, M. "Post-transplantation B cell function in different molecular types of SCID." Journal of Clinical Immunology 33.1 (2013): 96-110.
Source
scival
Published In
Journal of Clinical Immunology
Volume
33
Issue
1
Publish Date
2013
Start Page
96
End Page
110
DOI
10.1007/s10875-012-9797-6

Long-term outcome of non-ablative booster BMT in patients with SCID

SCID is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T cells. Immune reconstitution can be achieved through nonablative related donor BMT. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7% of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long-term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63%) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, P=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T-and B-cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Nonablative booster BMT can be lifesaving for SCID. © 2013 Macmillan Publishers Limited. All rights reserved.

Authors
Teigland, CL; Parrott, RE; Buckley, RH
MLA Citation
Teigland, CL, Parrott, RE, and Buckley, RH. "Long-term outcome of non-ablative booster BMT in patients with SCID." Bone Marrow Transplantation 48.8 (2013): 1050-1055.
Source
scival
Published In
Bone Marrow Transplantation
Volume
48
Issue
8
Publish Date
2013
Start Page
1050
End Page
1055
DOI
10.1038/bmt.2013.6

The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. © 2013 Springer Science+Business Media New York.

Authors
Dvorak, CC; Cowan, MJ; Logan, BR; Notarangelo, LD; Griffith, LM; Puck, JM; Kohn, DB; Shearer, WT; O'Reilly, RJ; Fleisher, TA; al, E
MLA Citation
Dvorak, CC, Cowan, MJ, Logan, BR, Notarangelo, LD, Griffith, LM, Puck, JM, Kohn, DB, Shearer, WT, O'Reilly, RJ, Fleisher, TA, and al, E. "The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901." Journal of Clinical Immunology (2013): 1-9.
PMID
23818196
Source
scival
Published In
Journal of Clinical Immunology
Publish Date
2013
Start Page
1
End Page
9
DOI
10.1007/s10875-013-9917-y

Primary Immune Deficiency Treatment Consortium (PIDTC) report

Authors
Griffith, LM; Cowan, MJ; Notarangelo, LD; Kohn, DB; Puck, JM; Pai, S-Y; Ballard, B; Bauer, SC; Bleesing, JJH; Boyle, M; Brower, A; Buckley, RH; van der Burg, M; Burroughs, LM; Candotti, F; Cant, AJ; Chatila, T; Cunningham-Rundles, C; Dinauer, MC; Dvorak, CC; Filipovich, AH; Fleisher, TA; Bobby Gaspar, H; Gungor, T; Haddad, E; Hovermale, E; Huang, F; Hurley, A; Hurley, M; Iyengar, S; Kang, EM; Logan, BR; Long-Boyle, JR; Malech, HL; McGhee, SA; Modell, F; Modell, V; Ochs, HD; O'Reilly, RJ et al.
MLA Citation
Griffith, LM, Cowan, MJ, Notarangelo, LD, Kohn, DB, Puck, JM, Pai, S-Y, Ballard, B, Bauer, SC, Bleesing, JJH, Boyle, M, Brower, A, Buckley, RH, van der Burg, M, Burroughs, LM, Candotti, F, Cant, AJ, Chatila, T, Cunningham-Rundles, C, Dinauer, MC, Dvorak, CC, Filipovich, AH, Fleisher, TA, Bobby Gaspar, H, Gungor, T, Haddad, E, Hovermale, E, Huang, F, Hurley, A, Hurley, M, Iyengar, S, Kang, EM, Logan, BR, Long-Boyle, JR, Malech, HL, McGhee, SA, Modell, F, Modell, V, Ochs, HD, and O'Reilly, RJ et al. "Primary Immune Deficiency Treatment Consortium (PIDTC) report." Journal of Allergy and Clinical Immunology (2013).
PMID
24139498
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Publish Date
2013

Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children with T-B-NK+ immunodeficiency.

Two infants are described who presented with 22q11.2 deletion and a T(-)B(-)NK(+) immune phenotype. For both infants, the initial diagnosis was athymia secondary to complete DiGeorge anomaly. The first infant underwent thymus transplantation but 6 months after transplantation had circulating thymus donor T cells; the patient did not develop recipient naïve T cells. Genetic analyses revealed that both patients had Artemis deficiency, a rare form of severe combined immunodeficiency (SCID). Both infants have subsequently undergone bone marrow transplantation. These cases illustrate the importance and paradox of differentiating SCID from complete DiGeorge anomaly because hematopoietic stem cell transplantation (HSCT) is the preferred treatment for SCID but is ineffective for complete DiGeorge anomaly. However, if the thymus is completely absent, donor stem cells from a HSCT would not be able to be educated.

Authors
Heimall, J; Keller, M; Saltzman, R; Bunin, N; McDonald-McGinn, D; Zakai, E; de Villartay, J-P; Moshous, D; Ariue, B; McCarthy, EA; Devlin, BH; Parikh, S; Buckley, RH; Markert, ML
MLA Citation
Heimall, J, Keller, M, Saltzman, R, Bunin, N, McDonald-McGinn, D, Zakai, E, de Villartay, J-P, Moshous, D, Ariue, B, McCarthy, EA, Devlin, BH, Parikh, S, Buckley, RH, and Markert, ML. "Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children with T-B-NK+ immunodeficiency." J Clin Immunol 32.5 (October 2012): 1141-1144.
PMID
22864628
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
32
Issue
5
Publish Date
2012
Start Page
1141
End Page
1144
DOI
10.1007/s10875-012-9741-9

CD45-deficient severe combined immunodeficiency caused by uniparental disomy.

Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient's mother was heterozygous for an inactivating mutation in CD45 but the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Nonlymphoid blood cells and other mesoderm- and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient, who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in seven additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings are unique in representing a reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.

Authors
Roberts, JL; Buckley, RH; Luo, B; Pei, J; Lapidus, A; Peri, S; Wei, Q; Shin, J; Parrott, RE; Dunbrack, RL; Testa, JR; Zhong, X-P; Wiest, DL
MLA Citation
Roberts, JL, Buckley, RH, Luo, B, Pei, J, Lapidus, A, Peri, S, Wei, Q, Shin, J, Parrott, RE, Dunbrack, RL, Testa, JR, Zhong, X-P, and Wiest, DL. "CD45-deficient severe combined immunodeficiency caused by uniparental disomy." Proc Natl Acad Sci U S A 109.26 (June 26, 2012): 10456-10461.
PMID
22689986
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
109
Issue
26
Publish Date
2012
Start Page
10456
End Page
10461
DOI
10.1073/pnas.1202249109

Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus.

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8(+) T cell subset, displayed a CD45RA(-)CCR7(-) effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8(+) SAP(+) T cells, but not SAP(-) cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.

Authors
Palendira, U; Low, C; Bell, AI; Ma, CS; Abbott, RJM; Phan, TG; Riminton, DS; Choo, S; Smart, JM; Lougaris, V; Giliani, S; Buckley, RH; Grimbacher, B; Alvaro, F; Klion, AD; Nichols, KE; Adelstein, S; Rickinson, AB; Tangye, SG
MLA Citation
Palendira, U, Low, C, Bell, AI, Ma, CS, Abbott, RJM, Phan, TG, Riminton, DS, Choo, S, Smart, JM, Lougaris, V, Giliani, S, Buckley, RH, Grimbacher, B, Alvaro, F, Klion, AD, Nichols, KE, Adelstein, S, Rickinson, AB, and Tangye, SG. "Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus." J Exp Med 209.5 (May 7, 2012): 913-924.
PMID
22493517
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
209
Issue
5
Publish Date
2012
Start Page
913
End Page
924
DOI
10.1084/jem.20112391

The long quest for neonatal screening for severe combined immunodeficiency.

Early recognition of severe combined immunodeficiency (SCID) is a pediatric emergency because a diagnosis before live vaccines or nonirradiated blood products are given and before development of infections permits lifesaving unfractionated HLA-identical or T cell-depleted haploidentical hematopoietic stem cell transplantation, enzyme replacement therapy, or gene therapy. The need for newborn screening for this condition has been recognized for the past 15 years. However, implementation of screening required development of an assay for T-cell lymphopenia that could be performed on dried bloodspots routinely collected from newborn infants for the past 48 years. This was accomplished 6 years ago, and there have already been 7 successful pilot studies. A recommendation to add SCID to the routine newborn-screening panel was approved by the Secretary's Advisory Committee on Heritable Disorders of Newborns and Children in 2010 and was soon after approved by the Secretary of Health and Human Services. It is important for allergists, immunologists, and other health care providers to take an active role in promoting newborn screening for SCID and other T-lymphocyte abnormalities in their states. Even more important will be their roles in establishing accurate diagnoses for infants with positive screen results and in ensuring that they are given the best possible treatment.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The long quest for neonatal screening for severe combined immunodeficiency." J Allergy Clin Immunol 129.3 (March 2012): 597-604. (Review)
PMID
22277203
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
129
Issue
3
Publish Date
2012
Start Page
597
End Page
604
DOI
10.1016/j.jaci.2011.12.964

CD45 Deficiency Caused by Uniparental Disomy, a Novel Cause of Severe Combined Immunodeficiency

Authors
Roberts, JL; Buckley, RH; Luo, B; Pei, J; Lapidus, A; Peri, S; Wei, Q; Shin, J; Parrott, RE; Dunbrack, R; Testa, JR; Zhong, X; Wiest, DL
MLA Citation
Roberts, JL, Buckley, RH, Luo, B, Pei, J, Lapidus, A, Peri, S, Wei, Q, Shin, J, Parrott, RE, Dunbrack, R, Testa, JR, Zhong, X, and Wiest, DL. "CD45 Deficiency Caused by Uniparental Disomy, a Novel Cause of Severe Combined Immunodeficiency." February 2012.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
129
Issue
2
Publish Date
2012
Start Page
AB84
End Page
AB84

Post-Transplantation B Cell Function in Different Molecular Types of SCID

Authors
Buckley, RH; Win, CM; Moser, BK; Parrott, RE; Sajaroff, E; Sarzotti-Kelsoe, M
MLA Citation
Buckley, RH, Win, CM, Moser, BK, Parrott, RE, Sajaroff, E, and Sarzotti-Kelsoe, M. "Post-Transplantation B Cell Function in Different Molecular Types of SCID." Journal of Clinical Immunology (2012): 1-15.
Website
http://hdl.handle.net/10161/11533
Source
scopus
Published In
Journal of Clinical Immunology
Publish Date
2012
Start Page
1
End Page
15

Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.

Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient patients often present also with nonimmunologic clinical problems, affecting the skeletal, central nervous, endocrine, and gastrointestinal systems. We now report that myeloid dysplasia features and bone marrow hypocellularity are often found in patients with ADA-SCID. As a clinical correlate to this finding, we have observed vulnerability to antibiotic-induced myelotoxicity and prolonged neutropenia after nonmyeloablative chemotherapy. We have also noted that, in the absence of enzyme replacement therapy, absolute neutrophil counts of patients with ADA deficiency vary inversely with the accumulation of deoxynucleotides. These data have significant implications for the application of standard and investigational therapies to patients with ADA-SCID and support further studies to investigate the possibility that ADA deficiency is associated with a stem cell defect. These trials were registered at www.clinicaltrials.gov as #NCT00018018 and #NCT00006319.

Authors
Sokolic, R; Maric, I; Kesserwan, C; Garabedian, E; Hanson, IC; Dodds, M; Buckley, R; Issekutz, AC; Kamani, N; Shaw, K; Tan, B; Bali, P; Hershfield, MS; Kohn, DB; Wayne, AS; Candotti, F
MLA Citation
Sokolic, R, Maric, I, Kesserwan, C, Garabedian, E, Hanson, IC, Dodds, M, Buckley, R, Issekutz, AC, Kamani, N, Shaw, K, Tan, B, Bali, P, Hershfield, MS, Kohn, DB, Wayne, AS, and Candotti, F. "Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency." Blood 118.10 (September 8, 2011): 2688-2694.
PMID
21725047
Source
pubmed
Published In
Blood
Volume
118
Issue
10
Publish Date
2011
Start Page
2688
End Page
2694
DOI
10.1182/blood-2011-01-329359

Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes.

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T- and B-cell function and, in some types, also of NK cells and function. Mutations in thirteen different genes have been found to cause this condition, which is uniformly fatal in the first 2 years of life unless immune reconstitution can be accomplished. In the 42 years since the first bone marrow transplant was given in 1968, the standard treatment for all forms of SCID has been allogeneic bone marrow transplantation. Both HLA-identical unfractionated and T-cell-depleted HLA-haploidentical bone marrow transplants have been very successful in effecting immune reconstitution, especially if performed in the first 3.5 months of life and without pre-transplant chemotherapy. This paper summarizes the longterm outcome, according to molecular type, of 166 consecutive SCID infants given non-conditioned related donor bone marrow transplants at this institution over the past 28.3 years and reviews published reports of longterm outcomes of transplants in SCID performed at other centers.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes." Immunol Res 49.1-3 (April 2011): 25-43. (Review)
PMID
21116871
Source
pubmed
Published In
Immunologic Research
Volume
49
Issue
1-3
Publish Date
2011
Start Page
25
End Page
43
DOI
10.1007/s12026-010-8191-9

The long and the short of telomeres in bone marrow recipient SCID patients.

Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant's vestigial thymus and to homeostatic proliferation of mature T cells in the peripheral organs. Since T-cell function, thymic output, and T-cell clonal diversity are maintained long term in these patients, we investigated whether donor T-cell engraftment resulted in increased telomere shortening. Our study of seven SCID patients, following successful bone marrow transplantation, demonstrates that the patients' peripheral T cells did not exhibit greater than normal telomere shortening.

Authors
Sarzotti-Kelsoe, M; Daniell, XG; Whitesides, JF; Buckley, RH
MLA Citation
Sarzotti-Kelsoe, M, Daniell, XG, Whitesides, JF, and Buckley, RH. "The long and the short of telomeres in bone marrow recipient SCID patients." Immunol Res 49.1-3 (April 2011): 44-48.
PMID
21120634
Source
pubmed
Published In
Immunologic Research
Volume
49
Issue
1-3
Publish Date
2011
Start Page
44
End Page
48
DOI
10.1007/s12026-010-8192-8

Why newborn screening for severe combined immunodeficiency is essential: a case report.

Physicians caring for infants in the first months of life need to know the normal ranges for absolute lymphocyte counts (ALCs) during that age. Any ALC <2500/microL is potentially pathogenic in early infancy and should be evaluated. We report the case of a 4-month-old white girl with a 2-month history of an oral ulcer, intermittent fever, recurrent otitis, decreased appetite, weight loss, and a new respiratory illness with hypoxemia. She had been in an in-home day care since birth. The patient's primary care physician had seen her frequently and obtained blood counts, but her persistent lymphopenia had not been appreciated. The infant was ultimately diagnosed with T(-)B(-)NK(+) (lacking both B and T lymphocytes and having primarily natural killer [NK] cells), recombinase-activating gene 2 (RAG2)-deficient severe combined immunodeficiency (SCID). However, because she had already developed 2 difficult-to-treat viral infections (parainfluenza 3 and adenovirus), she did not survive long enough to receive a bone marrow transplant. Newborn screening would not only have made the diagnosis at birth but would have led to measures to protect her from becoming infected before she could receive a transplant. Newborn screening would also reveal the true incidence of SCID and define the range of conditions characterized by severely impaired T-cell development. Until screening for SCID and other T-cell defects becomes available for all neonates (either by quantifying T-cell receptor excision circles in Guthrie spots or using other tests that quantify T cells), all pediatricians should know the normal range for ALCs according to age. Recognition of the characteristic lymphopenia of SCID can facilitate early diagnosis.

Authors
Adeli, MM; Buckley, RH
MLA Citation
Adeli, MM, and Buckley, RH. "Why newborn screening for severe combined immunodeficiency is essential: a case report." Pediatrics 126.2 (August 2010): e465-e469.
PMID
20603253
Source
pubmed
Published In
Pediatrics
Volume
126
Issue
2
Publish Date
2010
Start Page
e465
End Page
e469
DOI
10.1542/peds.2009-3659

B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review.

Although bone marrow transplantation has resulted in life-saving T-cell reconstitution in infants with severe combined immunodeficiency (SCID), correction of B-cell function has been more problematic. This review examines B-cell reconstitution results presented in 19 reports from the United States and Europe on posttransplantation immune reconstitution in patients with SCID over the past 2 decades. The analysis considered whether pretransplantation conditioning regimens were used, the overall survival rate, the percentage with donor B-cell chimerism, the percentage with B-cell function, and the percentage of survivors requiring immunoglobulin replacement. The survival rates were higher at those centers that did not use pretransplantation conditioning or posttransplantation graft-versus-host disease prophylaxis. The percentage of survivors with B-cell chimerism, function, or both was higher and the percentage requiring immunoglobulin replacement was lower at those centers that used pretransplantation conditioning. However, there were substantial numbers of patients requiring immunoglobulin replacement at all centers. Thus pretransplantation conditioning does not guarantee that B-cell function will develop. Because most infants with SCID either present with serious infections or are given diagnoses as newborns, one must decide whether there is justification for using agents that compromise innate immunity and have intrinsic toxicities to gain B-cell immune reconstitution.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review." J Allergy Clin Immunol 125.4 (April 2010): 790-797. (Review)
PMID
20371393
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
125
Issue
4
Publish Date
2010
Start Page
790
End Page
797
DOI
10.1016/j.jaci.2010.02.012

Digital microfluidics: a future technology in the newborn screening laboratory?

Expansion of newborn screening for inherited metabolic disorders using tandem mass spectrometry has generated interest in screening for other treatable conditions, including lysosomal storage diseases. Limitations to expansion include labor and equipment costs. We describe a cost-effective new platform that reduces the time to result reporting and can perform multiplexing assays requiring different platforms. Immunoassays and enzyme activity assays currently used in newborn screening have been translated to a disposable microchip programmed to dispense, transport, mix, wash, and incubate individual microdroplets from specimens, including dried blood spot extracts, and reagents all under software control. The specimen and reagents consumed are approximately 1% of those required by equivalent bench assays. In addition to immunologic and enzymatic assays, DNA amplification, amplicon detection, and sequencing have been demonstrated using the same microchips and control equipment. Recently, the multiplexing of 4 different enzyme activities has also been demonstrated with negligible cross-contamination. We review assays relevant to newborn screening.

Authors
Millington, DS; Sista, R; Eckhardt, A; Rouse, J; Bali, D; Goldberg, R; Cotten, M; Buckley, R; Pamula, V
MLA Citation
Millington, DS, Sista, R, Eckhardt, A, Rouse, J, Bali, D, Goldberg, R, Cotten, M, Buckley, R, and Pamula, V. "Digital microfluidics: a future technology in the newborn screening laboratory?." Semin Perinatol 34.2 (April 2010): 163-169.
PMID
20207266
Source
pubmed
Published In
Seminars in Perinatology
Volume
34
Issue
2
Publish Date
2010
Start Page
163
End Page
169
DOI
10.1053/j.semperi.2009.12.008

Transplantation immunology: solid organ and bone marrow.

Development of the field of organ and tissue transplantation has accelerated remarkably since the human MHC was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include antibodies, antigen-presenting cells, helper and cytotoxic T-cell subsets, immune cell-surface molecules, signaling mechanisms, and cytokines. The development of pharmacologic and biological agents that interfere with the alloimmune response has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid-organ transplantations include those of the kidneys, liver, heart, and lung. The use of bone marrow transplantation for hematologic diseases, particularly hematologic malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by means of infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in 2 forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation.

Authors
Chinen, J; Buckley, RH
MLA Citation
Chinen, J, and Buckley, RH. "Transplantation immunology: solid organ and bone marrow." J Allergy Clin Immunol 125.2 Suppl 2 (February 2010): S324-S335. (Review)
PMID
20176267
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
125
Issue
2 Suppl 2
Publish Date
2010
Start Page
S324
End Page
S335
DOI
10.1016/j.jaci.2009.11.014

Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management.

More than 20 North American academic centers account for the majority of hematopoietic stem cell transplantation (HCT) procedures for primary immunodeficiency diseases (PIDs), with smaller numbers performed at additional sites. Given the importance of a timely diagnosis of these rare diseases and the diversity of practice sites, there is a need for guidance as to best practices in management of patients with PIDs before, during, and in follow-up for definitive treatment. In this conference report of immune deficiency experts and HCT physicians who care for patients with PIDs, we present expert guidance for (1) PID diagnoses that are indications for HCT, including severe combined immunodeficiency disease (SCID), combined immunodeficiency disease, and other non-SCID diseases; (2) the critical importance of a high degree of suspicion of the primary care physician and timeliness of diagnosis for PIDs; (3) the need for rapid referral to an immune deficiency expert, center with experience in HCT, or both for patients with PIDs; (4) medical management of a child with suspicion of SCID/combined immunodeficiency disease while confirming the diagnosis, including infectious disease management and workup; (5) the posttransplantation follow-up visit schedule; (6) antimicrobial prophylaxis after transplantation, including gamma globulin administration; and (7) important indications for return to the transplantation center after discharge. Finally, we discuss the role of high-quality databases in treatment of PIDs and HCT as an element of the infrastructure that will be needed for productive multicenter clinical trials in these rare diseases.

Authors
Griffith, LM; Cowan, MJ; Notarangelo, LD; Puck, JM; Buckley, RH; Candotti, F; Conley, ME; Fleisher, TA; Gaspar, HB; Kohn, DB; Ochs, HD; O'Reilly, RJ; Rizzo, JD; Roifman, CM; Small, TN; Shearer, WT; Workshop Participants,
MLA Citation
Griffith, LM, Cowan, MJ, Notarangelo, LD, Puck, JM, Buckley, RH, Candotti, F, Conley, ME, Fleisher, TA, Gaspar, HB, Kohn, DB, Ochs, HD, O'Reilly, RJ, Rizzo, JD, Roifman, CM, Small, TN, Shearer, WT, and Workshop Participants, . "Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management." J Allergy Clin Immunol 124.6 (December 2009): 1152-60.e12.
PMID
20004776
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
124
Issue
6
Publish Date
2009
Start Page
1152
End Page
60.e12
DOI
10.1016/j.jaci.2009.10.022

Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis.

OBJECTIVE: To determine long-term health benefits of nonablative bone marrow transplantation for severe combined immunodeficiency (SCID), we investigated our cohort of 161 related donor bone marrow-transplanted patients with SCID. Only 16 (10%) had HLA-identical donors. STUDY DESIGN: All 124 survivors were sent questionnaires about their current clinical statuses. Details from clinic visits were also compiled. One hundred eleven patients (90%) were reached. We compared outcomes of patients transplanted before and after 3.5 months of life and by molecular defect. RESULTS: The overall survival rate was 77%, but the rate for the 48 infants transplanted in the first 3.5 months of life was 94%, compared with 70% for the 113 transplanted after 3.5 months (P = .002). Twenty-eight (76%) of the 37 deceased patients died of viral infections present at diagnosis. One or more clinical problems were reported to have been present in the past 2 years in 71 (64%) of the survivors, although 95 (86%) were considered healthy by their families. CONCLUSIONS: Most patients with SCID transplanted with related donor marrow without pretransplant chemotherapy have done well in the long term, but those transplanted at <3.5 months of age had a superior survival rate, a lower rate of clinical problems, less need for booster transplants, and better nutritional status.

Authors
Railey, MD; Lokhnygina, Y; Buckley, RH
MLA Citation
Railey, MD, Lokhnygina, Y, and Buckley, RH. "Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis." J Pediatr 155.6 (December 2009): 834-840.e1.
PMID
19818451
Source
pubmed
Published In
The Journal of Pediatrics
Volume
155
Issue
6
Publish Date
2009
Start Page
834
End Page
840.e1
DOI
10.1016/j.jpeds.2009.07.049

Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras.

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B, and sometimes NK-cell function. Nonablative human leukocyte antigen-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T-cell development in the recipients, leading to long-term survival. We reported previously that normal T-cell numbers, function, and repertoire developed by 3 to 4 months after transplantation in SCID patients, and the repertoire remained highly diverse for the first 10 years after BMT. The T-cell receptor diversity positively correlated with T-cell receptor excision circle levels, a reflection of thymic output. However, the fate of thymic function in SCID patients beyond 10 to 12 years after BMT remained to be determined. In this greater than 25-year follow-up study of 128 patients with 11 different molecular types of SCID after nonconditioned BMT, we provide evidence that T-cell function, thymic output, and T-cell clonal diversity are maintained long-term.

Authors
Sarzotti-Kelsoe, M; Win, CM; Parrott, RE; Cooney, M; Moser, BK; Roberts, JL; Sempowski, GD; Buckley, RH
MLA Citation
Sarzotti-Kelsoe, M, Win, CM, Parrott, RE, Cooney, M, Moser, BK, Roberts, JL, Sempowski, GD, and Buckley, RH. "Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras." Blood 114.7 (August 13, 2009): 1445-1453.
PMID
19433858
Source
pubmed
Published In
Blood
Volume
114
Issue
7
Publish Date
2009
Start Page
1445
End Page
1453
DOI
10.1182/blood-2009-01-199323

On Assessing Immunocompetence

Authors
Buckley, RH; Sidbury, JB
MLA Citation
Buckley, RH, and Sidbury, JB. "On Assessing Immunocompetence." February 2009.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
123
Issue
2
Publish Date
2009
Start Page
S3
End Page
S4

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)

Authors
Aiuti, A; Cattaneo, F; Galimberti, S; Benninghoff, U; Cassani, B; Callegaro, L; Scaramuzza, S; Andolfi, G; Mirolo, M; Brigida, I; Tabucchi, A; Carlucci, F; Eibl, M; Aker, M; Slavin, S; Al-Mousa, H; Al Ghonaium, A; Ferster, A; Duppenthaler, A; Notarangelo, L; Wintergerst, U; Buckley, RH; Bregni, M; Marktel, S; Valsecchi, MG; Rossi, P; Ciceri, F; Miniero, R; Bordignon, C; Roncarolo, M-G
MLA Citation
Aiuti, A, Cattaneo, F, Galimberti, S, Benninghoff, U, Cassani, B, Callegaro, L, Scaramuzza, S, Andolfi, G, Mirolo, M, Brigida, I, Tabucchi, A, Carlucci, F, Eibl, M, Aker, M, Slavin, S, Al-Mousa, H, Al Ghonaium, A, Ferster, A, Duppenthaler, A, Notarangelo, L, Wintergerst, U, Buckley, RH, Bregni, M, Marktel, S, Valsecchi, MG, Rossi, P, Ciceri, F, Miniero, R, Bordignon, C, and Roncarolo, M-G. "Gene therapy for immunodeficiency due to adenosine deaminase deficiency." N Engl J Med 360.5 (January 29, 2009): 447-458.
PMID
19179314
Source
pubmed
Published In
The New England journal of medicine
Volume
360
Issue
5
Publish Date
2009
Start Page
447
End Page
458
DOI
10.1056/NEJMoa0805817

On Assessing Immunocompetence

Authors
Buckley, RH; Sidbury, JB
MLA Citation
Buckley, RH, and Sidbury, JB. "On Assessing Immunocompetence." Journal of Allergy and Clinical Immunology 123.2 SUPPL. (2009): S3-S4.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
123
Issue
2 SUPPL.
Publish Date
2009
Start Page
S3
End Page
S4
DOI
10.1016/j.jaci.2008.11.028

Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs.

Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive HCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies.

Authors
Griffith, LM; Cowan, MJ; Kohn, DB; Notarangelo, LD; Puck, JM; Schultz, KR; Buckley, RH; Eapen, M; Kamani, NR; O'Reilly, RJ; Parkman, R; Roifman, CM; Sullivan, KE; Filipovich, AH; Fleisher, TA; Shearer, WT
MLA Citation
Griffith, LM, Cowan, MJ, Kohn, DB, Notarangelo, LD, Puck, JM, Schultz, KR, Buckley, RH, Eapen, M, Kamani, NR, O'Reilly, RJ, Parkman, R, Roifman, CM, Sullivan, KE, Filipovich, AH, Fleisher, TA, and Shearer, WT. "Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs." J Allergy Clin Immunol 122.6 (December 2008): 1087-1096.
PMID
18992926
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
122
Issue
6
Publish Date
2008
Start Page
1087
End Page
1096
DOI
10.1016/j.jaci.2008.09.045

Why newborn screening for severe combined immunodeficiency is essential: a case report

Authors
Adeli, M; Buckley, RH
MLA Citation
Adeli, M, and Buckley, RH. "Why newborn screening for severe combined immunodeficiency is essential: a case report." CLINICAL AND EXPERIMENTAL IMMUNOLOGY 154 (November 2008): 59-59.
Source
wos-lite
Published In
Clinical & Experimental Immunology
Volume
154
Publish Date
2008
Start Page
59
End Page
59

Long-term clinical outcome of patients with severe combined immunodeficiency (SCID) after non-ablative related donor bone marrow transplantation

Authors
Railey, M; Buckley, RH
MLA Citation
Railey, M, and Buckley, RH. "Long-term clinical outcome of patients with severe combined immunodeficiency (SCID) after non-ablative related donor bone marrow transplantation." February 2008.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
121
Issue
2
Publish Date
2008
Start Page
S82
End Page
S82
DOI
10.1016/j.jaci.2007.12.329

Family history and low absolute lymphocyte count (ALC) as diagnostic clues for severe combined immunodeficiency (SCID)

Authors
McWilliams, LM; McGoldrick, S; Railey, MD; Buckley, RH
MLA Citation
McWilliams, LM, McGoldrick, S, Railey, MD, and Buckley, RH. "Family history and low absolute lymphocyte count (ALC) as diagnostic clues for severe combined immunodeficiency (SCID)." February 2008.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
121
Issue
2
Publish Date
2008
Start Page
S166
End Page
S166
DOI
10.1016/j.jaci.2007.12.612

Population prevalence of diagnosed primary immunodeficiency diseases in the United States

Rationale: Although health surveys are routinely used to estimate the population incidence and prevalence of many chronic and acute conditions in the US population, they have infrequently been used for "rare" conditions such as primary immunodeficiency diseases (PID). Accurate prevalence measures are needed to separate the truly rare condition from those that primary care doctors are likely to see in their practices today, if early diagnosis and treatment are to be achieved. Methods: A national probability sample of 10,000 households was sampled by random digit dialing and screened by telephone to identify how many of the nearly 27,000 household members had been diagnosed with a PID. Results: A total of 23 household members in 18 households were reported with a specific diagnosis for PID (CVID, IgA, IgG, XLA, SCID, CGD), whereas additional cases were reported as a PID without a confirmatory diagnosis. These findings suggest a population prevalence of diagnosed PID in the United States at approximately 1 in 1,200 persons. Conclusions: Diagnoses of PID in the United States are far more common than suggested in the literature. © 2008 Network of Centres for Study of Pharmaceutical Law.

Authors
Boyle, JM; Buckley, RH
MLA Citation
Boyle, JM, and Buckley, RH. "Population prevalence of diagnosed primary immunodeficiency diseases in the United States." Pharmaceuticals Policy and Law 10 (January 1, 2008): 99-108.
Source
scopus
Published In
Pharmaceuticals Policy and Law
Volume
10
Publish Date
2008
Start Page
99
End Page
108

The effect of natural killer cell killer ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID) (vol 27, pg 659, 2007)

Authors
Keller, MD; Chen, DF; Condron, SA; Liu, N; Reinsmoen, NL; Buckley, RH
MLA Citation
Keller, MD, Chen, DF, Condron, SA, Liu, N, Reinsmoen, NL, and Buckley, RH. "The effect of natural killer cell killer ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID) (vol 27, pg 659, 2007)." JOURNAL OF CLINICAL IMMUNOLOGY 27.6 (November 2007): 659-659.
Source
wos-lite
Published In
Journal of Clinical Immunology
Volume
27
Issue
6
Publish Date
2007
Start Page
659
End Page
659
DOI
10.1007/s10875-007-9116-9

Population prevalence of diagnosed primary immunodeficiency diseases in the United States.

RATIONALE: Although health surveys are routinely used to estimate the population incidence and prevalence of many chronic and acute conditions in the U.S. population, they have infrequently been used for "rare" conditions such as primary immunodeficiency diseases (PID). Accurate prevalence measures are needed to separate the truly rare condition from those that primary care doctors are likely to see in their practices today, if early diagnosis and treatment are to be achieved. METHODS: A national probability sample of 10,000 households was sampled by random digit dialing and screened by telephone to identify how many of the nearly 27,000 household members had been diagnosed with a PID. RESULTS: A total of 23 household members in 18 households were reported with a specific diagnosis for PID (CVID, IgA, IgG, XLA, SCID, CGD), whereas additional cases were reported as a PID without a confirmatory diagnosis. These findings suggest a population prevalence of diagnosed PID in the United States at approximately 1 in 1,200 persons. CONCLUSIONS: Diagnoses of PID in the United States are far more common than suggested in the literature.

Authors
Boyle, JM; Buckley, RH
MLA Citation
Boyle, JM, and Buckley, RH. "Population prevalence of diagnosed primary immunodeficiency diseases in the United States." J Clin Immunol 27.5 (September 2007): 497-502.
PMID
17577648
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
27
Issue
5
Publish Date
2007
Start Page
497
End Page
502
DOI
10.1007/s10875-007-9103-1

Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency.

The persistence of transplacentally transferred maternal T cells is common in infants with severe combined immunodeficiency (SCID), occurring in more than half of patients with SCID undergoing transplantation at our institution. These T cells respond poorly to mitogens in vitro but can cause cutaneous graft-versus-host disease; however, other effects of these cells are unknown. We describe 2 infants with SCID who had unusual problems associated with transplacentally transferred maternal T cells. Patient 1 was a 5-month-old girl with Janus kinase 3-deficient SCID who had 4% circulating CD3(+) T cells but no lymphocyte proliferative response to mitogens. Although the number of T cells increased after 2 nonchemoablated, T cell-depleted, haploidentical, paternal bone marrow transplantations, T-cell function failed to develop, and she became pancytopenic. Restriction fragment length polymorphism studies of flow cytometry-sorted blood T cells revealed all to be of maternal origin. A subsequent nonchemoablated, T cell-depleted maternal transplantation resulted in normal T-cell function and marrow recovery. Patient 2 was a 9-month-old girl with IL-7Ralpha-deficient SCID who presented with autoimmune pancytopenia. She had 8% blood T cells (all CD45RO(+)) but no response to mitogens. High-resolution HLA sequence-specific priming typing detected both maternal haplotypes, indicating the presence of maternal cells. Her pancytopenia resolved after treatment with rituximab and was thought to be due to host B-cell activation by transplacentally acquired maternal T cells. Persistent transplacentally acquired maternal T cells in infants with SCID can mediate immunologic functions despite failing to respond to mitogens in vitro. We present evidence that these cells can cause allograft rejection and immune cytopenias.

Authors
Palmer, K; Green, TD; Roberts, JL; Sajaroff, E; Cooney, M; Parrott, R; Chen, D-F; Reinsmoen, NL; Buckley, RH
MLA Citation
Palmer, K, Green, TD, Roberts, JL, Sajaroff, E, Cooney, M, Parrott, R, Chen, D-F, Reinsmoen, NL, and Buckley, RH. "Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency." J Allergy Clin Immunol 120.2 (August 2007): 423-428.
PMID
17481714
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
120
Issue
2
Publish Date
2007
Start Page
423
End Page
428
DOI
10.1016/j.jaci.2007.02.047

T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.

CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3zeta gene. The few T cells present contained no detectable CD3zeta protein, expressed low levels of cell surface CD3epsilon, and were nonfunctional. CD4(+)CD8(-)CD3epsilon(low), CD4(-)CD8(+)CD3epsilon(low), and CD4(-)CD8(-)CD3epsilon(low) cells were detected in the periphery, and the patient also exhibited an unusual population of CD56(-)CD16(+) NK cells with diminished cytolytic activity. Additional studies demonstrated that retrovirally transduced patient mutant CD3zeta cDNA failed to rescue assembly of nascent complete TCR complexes or surface TCR expression in CD3zeta-deficient MA5.8 murine T-cell hybridoma cells. Nascent transduced mutant CD3zeta protein was also not detected in metabolically labeled MA5.8 cells, suggesting that it was unstable and rapidly degraded. Taken together, these findings provide the first demonstration that complete CD3zeta deficiency in humans can cause SCID by preventing normal TCR assembly and surface expression.

Authors
Roberts, JL; Lauritsen, JPH; Cooney, M; Parrott, RE; Sajaroff, EO; Win, CM; Keller, MD; Carpenter, JH; Carabana, J; Krangel, MS; Sarzotti, M; Zhong, X-P; Wiest, DL; Buckley, RH
MLA Citation
Roberts, JL, Lauritsen, JPH, Cooney, M, Parrott, RE, Sajaroff, EO, Win, CM, Keller, MD, Carpenter, JH, Carabana, J, Krangel, MS, Sarzotti, M, Zhong, X-P, Wiest, DL, and Buckley, RH. "T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex." Blood 109.8 (April 15, 2007): 3198-3206.
PMID
17170122
Source
pubmed
Published In
Blood
Volume
109
Issue
8
Publish Date
2007
Start Page
3198
End Page
3206
DOI
10.1182/blood-2006-08-043166

Epstein-Barr-associated leiomyomatosis and T-cell chimerism after haploidentical bone marrow transplantation for severe combined immunodeficiency disease.

BACKGROUND: The clinical course of Epstein-Barr virus (EBV)-associated smooth muscle tumors is variable and there are no reports in patients with mixed T-cell chimerism after bone marrow transplantation (BMT). OBSERVATIONS: A child with X-linked severe combined immunodeficiency disease developed multiple renal and pulmonary leiomyomata 8 years after haploidentical BMT. Epstein-Barr viral DNA was detectable in the blood and in situ hybridization for EBV-encoded RNAs was positive in the tumor. The tumors have been radiographically stable, chimerism remains mixed, and plasma EBV DNA has been repeatedly negative for over 2 years after donor lymphocyte infusion. CONCLUSIONS: EBV-associated smooth muscle tumors may occur in patients who are partially reconstituted after BMT for severe combined immunodeficiency and may not require surgery or chemotherapy.

Authors
Atluri, S; Neville, K; Davis, M; Robertson, KA; Marshalleck, FE; O'Malley, DP; Buckley, RH; Nelson, RP
MLA Citation
Atluri, S, Neville, K, Davis, M, Robertson, KA, Marshalleck, FE, O'Malley, DP, Buckley, RH, and Nelson, RP. "Epstein-Barr-associated leiomyomatosis and T-cell chimerism after haploidentical bone marrow transplantation for severe combined immunodeficiency disease." J Pediatr Hematol Oncol 29.3 (March 2007): 166-172.
PMID
17356396
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
29
Issue
3
Publish Date
2007
Start Page
166
End Page
172
DOI
10.1097/MPH.0b013e31803b95b3

The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID).

Natural killer (NK) cell alloreactions against recipient cells in the setting of bone marrow transplantation have been associated with decreased rates of graft-versus-host disease (GVHD) and improved survival in transplant recipients with myeloid leukemia. These alloreactions are predicted by the absence of recipient HLA class I ligands for donor inhibitory killer Ig-like receptors (KIR). We hypothesized that donor NK cell alloreactions against recipient cells may affect the development of T and B-cell functions and incidence of GVHD in infants with severe combined immunodeficiency (SCID). Of the 156 patients with SCID who had received related bone marrow transplants without pretransplant chemotherapy or posttransplant GVHD prophylaxis, 137 patient-donor pairs were evaluated for the absence of recipient HLA class I ligands for donor inhibitory KIR. Analysis showed that the absence of a KIR ligand had no effect on the incidence or severity of GVHD (RR [corrected] = 0.95, p = 0.84), development of T-cell function (RR [corrected] = 1.05, p = 0.69), production of IgA (p = 0.46) or IgM (p = 0.33), or on 5-year survival (RR [corrected] = 1.21, p = 0.10). Further, in patients possessing native NK cells, the absence of KIR ligands in donors for recipient-inhibitory KIR did not alter transplantation outcomes. This study suggests that inhibitory KIR/HLA interactions do not play a significant role in bone marrow transplantation for SCID.

Authors
Keller, MD; Chen, DF; Condron, SA; Liu, N; Reinsmoen, NL; Buckley, RH
MLA Citation
Keller, MD, Chen, DF, Condron, SA, Liu, N, Reinsmoen, NL, and Buckley, RH. "The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID)." J Clin Immunol 27.1 (January 2007): 109-116.
PMID
17191149
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
27
Issue
1
Publish Date
2007
Start Page
109
End Page
116
DOI
10.1007/s10875-006-9058-7

Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006)

Adenosine deaminase (ADA) deficiency is a disorder of purine salvage that has its most devastating consequences in the immune system leading to severe combined immunodeficiency (SCID). Management options for ADA SCID include hematopoietic stem cell transplantation, enzyme replacement therapy and gene therapy. Formal data on the outcome following each of the three treatment modalities are limited, and this symposium was held in order to gather together the experience from major centers in Europe and the US. Transplantation for ADA-SCID is highly successful with survival rates of ∼ 90% if a matched sibling or matched related donor is available but survival following matched unrelated donor or haploidentical procedures is 63% and 50% respectively with a significant rejection/non-engraftment rate in unconditioned procedures. Successfully transplanted patients demonstrated good immunological recovery with normal cellular and humoral function in the majority of cases. PEG-ADA has been used in over 150 patients worldwide either as an alternative to mismatched transplant or as a stabilizing measure prior to transplant. Overall, approximately two thirds of patients treated with PEG-ADA have survived with the majority of patients showing good clinical improvement. The level of immune recovery long term was less than that seen after transplant and ∼ 50% of patients continued to receive immunoglobulin replacement. Gene therapy has been used as an experimental procedure in two centers in Europe. Early results from 9 patients suggest that the treatment is safe and that the majority have shown recovery of cellular immune function. Long-term follow-up of treated patients highlights a significant incidence of non-immunological problems with cognitive, neurological and audiological abnormalities most prominent. © 2006 Elsevier Inc. All rights reserved.

Authors
Booth, C; Hershfield, M; Notarangelo, L; Buckley, R; Hoenig, M; Mahlaoui, N; Cavazzana-Calvo, M; Aiuti, A; Gaspar, HB
MLA Citation
Booth, C, Hershfield, M, Notarangelo, L, Buckley, R, Hoenig, M, Mahlaoui, N, Cavazzana-Calvo, M, Aiuti, A, and Gaspar, HB. "Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006)." Clinical Immunology 123.2 (2007): 139-147.
PMID
17300989
Source
scival
Published In
Clinical Immunology
Volume
123
Issue
2
Publish Date
2007
Start Page
139
End Page
147
DOI
10.1016/j.clim.2006.12.009

Primary immunodeficiency or not? Making the correct diagnosis.

Making a correct diagnosis of a primary immunodeficiency disease is crucial for the selection of proper therapy. Although many cases go undiagnosed, there are also many instances of incorrect diagnosis that result in years of inappropriate treatment and failure to implement beneficial treatment. This article summarizes 2 actual cases in which incorrect diagnoses led to recommendations of unwarranted high-risk or costly treatments. Had the physicians chosen tests of immune function rather than relying on immunoglobulin levels or cell counts, they would have arrived at the true diagnoses.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Primary immunodeficiency or not? Making the correct diagnosis." J Allergy Clin Immunol 117.4 (April 2006): 756-758.
PMID
16630930
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
117
Issue
4
Publish Date
2006
Start Page
756
End Page
758
DOI
10.1016/j.jaci.2006.01.008

Natural killer T (NKT) cell development in severe combined immunodeficiency (SCID) after T cell depleted haploidentical bone marrow transplantation (BMT)

Authors
Sajaroff, EO; Buckley, RH
MLA Citation
Sajaroff, EO, and Buckley, RH. "Natural killer T (NKT) cell development in severe combined immunodeficiency (SCID) after T cell depleted haploidentical bone marrow transplantation (BMT)." February 2006.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
117
Issue
2
Publish Date
2006
Start Page
S325
End Page
S325
DOI
10.1016/j.jaci.2005.12.1282

Population prevalence of diagnosed primary immune deficiency diseases in the United States

Authors
Boyle, JM; Buckley, RH
MLA Citation
Boyle, JM, and Buckley, RH. "Population prevalence of diagnosed primary immune deficiency diseases in the United States." February 2006.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
117
Issue
2
Publish Date
2006
Start Page
S105
End Page
S105
DOI
10.1016/j.jaci.2005.12.422

Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology

Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.

Authors
Orange, JS; Hossny, EM; Weiler, CR; Ballow, M; Berger, M; Bonilla, FA; Buckley, R; Chinen, J; El-Gamal, Y; Mazer, BD; Jr, RPN; Patel, DD; Secord, E; Sorensen, RU; Wasserman, RL; Cunningham-Rundles, C
MLA Citation
Orange, JS, Hossny, EM, Weiler, CR, Ballow, M, Berger, M, Bonilla, FA, Buckley, R, Chinen, J, El-Gamal, Y, Mazer, BD, Jr, RPN, Patel, DD, Secord, E, Sorensen, RU, Wasserman, RL, and Cunningham-Rundles, C. "Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology." Journal of Allergy and Clinical Immunology 117.4 SUPPL. (2006): S525-S553.
PMID
16580469
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
117
Issue
4 SUPPL.
Publish Date
2006
Start Page
S525
End Page
S553
DOI
10.1016/j.jaci.2006.01.015

Variable phenotypic expression of mutations in genes of the immune system.

Discovery of mutated genes that cause various types of primary immunodeficiencies has significantly advanced our understanding of the pathogenesis of these diseases and of the functions of normal gene products. However, it is becoming abundantly clear that the phenotypic presentation of mutations in a given gene can be quite different, depending upon the location and type of mutation but also probably upon other genetic factors and environmental influences. In this issue of the JCI, de Villartay et al. describe a third phenotype for mutations in recombination activating gene 1 (RAG1), in addition to the already known phenotypes of SCID and Omenn syndrome (see the related article beginning on page 3291).

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Variable phenotypic expression of mutations in genes of the immune system." J Clin Invest 115.11 (November 2005): 2974-2976. (Review)
PMID
16276411
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
115
Issue
11
Publish Date
2005
Start Page
2974
End Page
2976
DOI
10.1172/JCI26956

EBVassociated leiomyomas following haploidentical transplantation for X-linked severe combined immunodeficiency disease

Authors
Robertson, KA; Alturi, S; Neville, K; Davis, M; Marshalleck, FE; Buckley, RH; Nelson, RP
MLA Citation
Robertson, KA, Alturi, S, Neville, K, Davis, M, Marshalleck, FE, Buckley, RH, and Nelson, RP. "EBVassociated leiomyomas following haploidentical transplantation for X-linked severe combined immunodeficiency disease." February 2005.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
82
End Page
82
DOI
10.1016/j.bbmt.2004.12.241

Ex vivo gene therapy of a preadolescent with x-linked severe combined immunodeficiency

Authors
Chinen, J; Puck, JM; Davis, J; Linton, GF; Whiting-Theobald, NL; Woltz, PC; Buckley, RH; Malech, HL
MLA Citation
Chinen, J, Puck, JM, Davis, J, Linton, GF, Whiting-Theobald, NL, Woltz, PC, Buckley, RH, and Malech, HL. "Ex vivo gene therapy of a preadolescent with x-linked severe combined immunodeficiency." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
120A
End Page
120A

The multiple causes of human SCID.

SCID, a syndrome characterized by the absence of T cells and adaptive immunity, can result from mutations in multiple genes that encode components of the immune system. Three such components are cytokine receptor chains or signaling molecules, five are needed for antigen receptor development, one is adenosine deaminase--a purine salvage pathway enzyme, and the last is a phosphatase, CD45. In this issue of the JCI, a report describes how complete deficiency of the CD3epsilon chain of the T cell antigen receptor/CD3 complex causes human SCID.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The multiple causes of human SCID." J Clin Invest 114.10 (November 2004): 1409-1411.
PMID
15545990
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
114
Issue
10
Publish Date
2004
Start Page
1409
End Page
1411
DOI
10.1172/JCI23571

A novel mutation in IFN-gamma receptor 2 with dominant negative activity: biological consequences of homozygous and heterozygous states.

We identified two siblings homozygous for a single base pair deletion in the IFN-gammaR2 transmembrane domain (791delG) who presented with multifocal Mycobacterium abscessus osteomyelitis (patient 1) and disseminated CMV and Mycobacterium avium complex infection (patient 2), respectively. Although the patients showed no IFN-gammaR activity, their healthy heterozygous parents showed only partial IFN-gammaR activity. An HLA-identical bone marrow transplant from the mother led patient 1 to complete hemopoietic reconstitution, but only partial IFN-gammaR function. We cloned and expressed fluorescent fusion proteins of the wild-type IFN-gammaR2, an IFN-gammaR2 mutant previously described to produce a complete autosomal recessive deficiency (278del2), and of 791delG to determine whether the intermediate phenotype in the 791delG heterozygous state was caused by haploinsufficiency or a dominant negative effect. When cotransfected together with the wild-type vector into IFN-gammaR2-deficient fibroblasts, the fusion protein with 791delG inhibited IFN-gammaR function by 48.7 +/- 5%, whereas fusion proteins with 278del2 had no inhibitory effect. Confocal microscopy of 791delG fusion proteins showed aberrant diffuse intracellular accumulation without plasma membrane localization. The fusion protein created by 791delG did not complete Golgi processing, and was neither expressed on the plasma membrane, nor shed extracellularly. The mutant construct 791delG exerts dominant negative effects on IFN-gamma signaling without cell surface display, suggesting that it is acting on pathways other than those involved in cell surface recognition of ligand.

Authors
Rosenzweig, SD; Dorman, SE; Uzel, G; Shaw, S; Scurlock, A; Brown, MR; Buckley, RH; Holland, SM
MLA Citation
Rosenzweig, SD, Dorman, SE, Uzel, G, Shaw, S, Scurlock, A, Brown, MR, Buckley, RH, and Holland, SM. "A novel mutation in IFN-gamma receptor 2 with dominant negative activity: biological consequences of homozygous and heterozygous states." J Immunol 173.6 (September 15, 2004): 4000-4008.
PMID
15356149
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
173
Issue
6
Publish Date
2004
Start Page
4000
End Page
4008

Jak3 and the pathogenesis of severe combined immunodeficiency.

The discovery that Jak3 mutations are a significant cause of severe combined immunodeficiency (SCID), a rare inherited defect characterized by lymphopenia, has provided valuable insights into the functions of Jak3 in lymphoid development and function. The current therapy for patients suffering from Jak3 SCID is hematopoetic stem cell transplantation, although gene therapy trials have also been performed. In lieu of crystal structure data, these patient-derived mutations have aided in the elucidation of the functions of various structural components of Jak3. By virtue of its requirement for lymphoid functions, Jak3 makes a tantalizing target for immunosuppression and anti-cancer therapy. Herein, we discuss the normal actions of the gammac cytokines, the pathogenesis and treatment protocols for SCID, and finally, the production of a new, selective Jak3 inhibitor capable of preventing transplant rejection in two animal models. Further study of Jak3 will hopefully provide insights into the clinical treatment of patients suffering from immune-mediated diseases.

Authors
O'Shea, JJ; Husa, M; Li, D; Hofmann, SR; Watford, W; Roberts, JL; Buckley, RH; Changelian, P; Candotti, F
MLA Citation
O'Shea, JJ, Husa, M, Li, D, Hofmann, SR, Watford, W, Roberts, JL, Buckley, RH, Changelian, P, and Candotti, F. "Jak3 and the pathogenesis of severe combined immunodeficiency." Mol Immunol 41.6-7 (July 2004): 727-737. (Review)
PMID
15220007
Source
pubmed
Published In
Molecular Immunology
Volume
41
Issue
6-7
Publish Date
2004
Start Page
727
End Page
737
DOI
10.1016/j.molimm.2004.04.014

A historical review of bone marrow transplantation for immunodeficiencies.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "A historical review of bone marrow transplantation for immunodeficiencies." J Allergy Clin Immunol 113.4 (April 2004): 793-800. (Review)
PMID
15100688
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
113
Issue
4
Publish Date
2004
Start Page
793
End Page
800
DOI
10.1016/j.jaci.2004.01.764

Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases.

BACKGROUND: Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. OBJECTIVE: The purpose of this study was to determine whether the patients had significant immunodeficiency. METHODS: Research testing of peripheral blood included immunoscope evaluation of T-cell receptor beta variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). RESULTS: The patients were classified as having DiGeorge syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells (<50/mm(3)) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. CONCLUSION: Patients with DiGeorge syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor beta variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.

Authors
Markert, ML; Alexieff, MJ; Li, J; Sarzotti, M; Ozaki, DA; Devlin, BH; Sempowski, GD; Rhein, ME; Szabolcs, P; Hale, LP; Buckley, RH; Coyne, KE; Rice, HE; Mahaffey, SM; Skinner, MA
MLA Citation
Markert, ML, Alexieff, MJ, Li, J, Sarzotti, M, Ozaki, DA, Devlin, BH, Sempowski, GD, Rhein, ME, Szabolcs, P, Hale, LP, Buckley, RH, Coyne, KE, Rice, HE, Mahaffey, SM, and Skinner, MA. "Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases." J Allergy Clin Immunol 113.4 (April 2004): 734-741.
PMID
15100681
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
113
Issue
4
Publish Date
2004
Start Page
734
End Page
741
DOI
10.1016/j.jaci.2004.01.766

Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation.

We found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, all infants presented with a T-B+NK- phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)-dependent interleukin-2 (IL-2)-induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect c association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions.

Authors
Roberts, JL; Lengi, A; Brown, SM; Chen, M; Zhou, Y-J; O'Shea, JJ; Buckley, RH
MLA Citation
Roberts, JL, Lengi, A, Brown, SM, Chen, M, Zhou, Y-J, O'Shea, JJ, and Buckley, RH. "Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation." Blood 103.6 (March 15, 2004): 2009-2018.
PMID
14615376
Source
pubmed
Published In
Blood
Volume
103
Issue
6
Publish Date
2004
Start Page
2009
End Page
2018
DOI
10.1182/blood-2003-06-2104

Abnormal development of thymic dendritic and epithelial cells in human X-linked severe combined immunodeficiency.

The X-linked form of severe combined immunodeficiency (X-SCID) is caused by mutations in the common cytokine receptor gamma chain and results in lack of T and NK cells and defective B cells. Without immune reconstitution, X-SCID patients typically die from infection during infancy. This report describes thymic epithelial (TE), lymphocyte, and dendritic cell (DC) differentiation in the thymic microenvironment of seven X-SCID patients who died before or after treatment for their immunodeficiency. X-SCID thymus consisted predominately of TE cells without grossly evident corticomedullary distinction. CD3+ and CD1a+ developing T cells and CD83+ thymic DC were reduced >50-fold when compared to age- and gender-matched control thymus (P < 0.001). TE expression of epithelial differentiation markers CK14, involucrin, and high molecular weight cytokeratins also differed in X-SCID versus normal thymus. These histopathologic findings indicate that in addition to T cells, thymic DC development and differentiation of TE cells are also abnormal in X-SCID.

Authors
Hale, LP; Buckley, RH; Puck, JM; Patel, DD
MLA Citation
Hale, LP, Buckley, RH, Puck, JM, and Patel, DD. "Abnormal development of thymic dendritic and epithelial cells in human X-linked severe combined immunodeficiency." Clin Immunol 110.1 (January 2004): 63-70.
PMID
14962797
Source
pubmed
Published In
Clinical Immunology
Volume
110
Issue
1
Publish Date
2004
Start Page
63
End Page
70
DOI
10.1016/j.clim.2003.09.002

Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution.

Mutations in nine different genes have been found to cause the human severe combined immunodeficiency syndrome. The products of three of the genes--IL-2RG, Jak3, and IL-7R alpha--are components of cytokine receptors, and the products of three more-RAG1, RAG2, and Artemis-are essential for effecting antigen receptor gene rearrangement. Additionally, a deficiency of CD3 delta, a component of the T-cell antigen receptor, results in a near absence of circulating mature CD3+ T cells and a complete lack of gamma/delta T cells. Adenosine deaminase deficiency results in toxic accumulations of metabolites that cause T cell apoptosis. Finally, a deficiency of CD45, a critical regulator of signaling thresholds in immune cells, also causes SCID. Approaches to immune reconstitution have included bone marrow transplantation and gene therapy. Bone marrow transplantation, both HLA identical unfractionated and T cell-depleted HLA haploidentical, has been very successful in effecting immune reconstitution if done in the first 3.5 months of life and without pretransplant chemotherapy. Gene therapy was highly successful in nine infants with X-linked SCID, but the trials have been placed on hold due to the development of a leukemic process in two of the children because of insertional oncogenesis.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution." Annu Rev Immunol 22 (2004): 625-655. (Review)
PMID
15032591
Source
pubmed
Published In
Annual Review of Immunology
Volume
22
Publish Date
2004
Start Page
625
End Page
655
DOI
10.1146/annurev.immunol.22.012703.104614

Pulmonary complications of primary immunodeficiencies.

In the fifty years since Ogden Bruton discovered agammaglobulinemia, more than 100 additional immunodeficiency syndromes have been described. These disorders may involve one or more components of the immune system, including T, B, and NK lymphocytes; phagocytic cells; and complement proteins. Most are recessive traits, some of which are caused by mutations in genes on the X chromosome, others in genes on autosomal chromosomes. Until the past decade, there was little insight into the fundamental problems underlying a majority of these conditions. Many of the primary immunodeficiency diseases have now been mapped to specific chromosomal locations, and the fundamental biologic errors have been identified in more than 3 dozen. Within the past decade the molecular bases of 7 X-linked immunodeficiency disorders have been reported: X-linked immunodeficiency with Hyper IgM, X-linked lymphoproliferative disease, X-linked agammaglobulinemia, X-linked severe combined immunodeficiency, the Wiskott-Aldrich syndrome, nuclear factor kappaB essential modulator (NEMO or IKKg), and the immune dysregulation polyendocrinopathy (IPEX) syndrome. The abnormal genes in X-linked chronic granulomatous disease (CGD) and properdin deficiency had been identified several years earlier. In addition, there are now many autosomal recessive immunodeficiencies for which the molecular bases have been discovered. These new advances will be reviewed, with particular emphasis on the pulmonary complications of some of these diseases. In some cases there are unique features of lung abnormalities in specific defects. Infections obviously account for most of these complications, but the host reaction to infection often leads to characteristic findings that can be helpful diagnostically. Finally, advances in treatment of the underlying diseases as well as their infectious complications will be covered.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Pulmonary complications of primary immunodeficiencies." Paediatr Respir Rev 5 Suppl A (2004): S225-S233. (Review)
PMID
14980276
Source
pubmed
Published In
Paediatric Respiratory Reviews
Volume
5 Suppl A
Publish Date
2004
Start Page
S225
End Page
S233

Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, IMG1, IMG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review

Severe combined immunodeficiency (SCID) is an inherited immune disorder characterized by T-cell lymphopenia (TCLP), a profound lack of cellular (T-cell) and humoral (B-cell) immunity and, in some cases, decreased NK-cell number and function. Affected children develop severe bacterial and viral infections within the first 6 months of life and die before 1 year of age without treatment. Mutations in any of eight known genes: IL2RG, ARTEMIS, RAG1, RAG2, ADA, CD45, JAK3, and IL7R cause SCID. Mutations in unidentified genes may also cause SCID. Population-based genotype and allelic frequencies of these gene defects have not been measured. Some minimal estimates of SCID prevalence are presented. Currently, hematopoietic stem cell transplants are the standard treatment. In clinical trials, gene therapy has been used to reconstitute immune function in patients with IL2RG and ADA defects. The availability of effective therapies, plus the short asymptomatic period after birth, (when stem-cell transplantation is most effective), make SCID a potentially good candidate for newborn screening. Dried blood spots are currently collected from all infants at birth for newborn metabolic screening. Tests for TCLP on dried blood spots could be developed as a screen for SCID. Because SCID may be unrecognized, with infant deaths from infection attributed to other causes, newborn screening is the only way to ascertain true birth prevalence. Validated tests and pilot population studies are necessary to determine newborn screening's potential for identifying infants with SCID.

Authors
Kalman, L; Lindegren, ML; Kobrynski, L; Vogt, R; Hannon, H; Howard, JT; Buckley, R
MLA Citation
Kalman, L, Lindegren, ML, Kobrynski, L, Vogt, R, Hannon, H, Howard, JT, and Buckley, R. "Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, IMG1, IMG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review." Genetics in Medicine 6.1 (2004): 16-26.
PMID
14726805
Source
scival
Published In
Genetics in Medicine
Volume
6
Issue
1
Publish Date
2004
Start Page
16
End Page
26
DOI
10.1097/01.GIM.0000105752.80592.A3

The use of intravenous immunoglobulin for allogeneic stem cell transplantation: the US experience

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The use of intravenous immunoglobulin for allogeneic stem cell transplantation: the US experience." 2004.
Source
wos-lite
Published In
INTRAVENOUS IMMUNOGLOBULINS IN THE THIRD MILLENNIUM
Publish Date
2004
Start Page
81
End Page
84

Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial.

A novel method of large-scale chromatography has been developed to improve recovery and purity of immunoglobulin G (IgG) from pooled plasma. The current study compares safety, toxicity and efficacy of two intravenous immunoglobulin products: a novel formulation, IGIV caprylate/chromatography (IGIV-C; Gamunex, 10%) and a licensed solvent/detergent-treated product, Gamimune N, 10% (IGIV-SD). The study, a randomized, double-blind, parallel group, therapeutic equivalence trial, was conducted at 25 treatment centers in Canada and the United States. Patients (n=172) having confirmed chronic primary immunodeficiency (PID), aged 1-75 years, and receiving IGIV therapy were enrolled. For 9 months, patients were treated with IGIV-C or IGIV-SD in accordance with the patient's individualized treatment regimen utilized before study entry. The primary endpoint was the proportion of patients with >or=1 validated acute sinopulmonary infection during the treatment period. Secondary endpoints included the proportion of patients with all infections, time to first infection, annual infection rates, lung function parameters, infusion-related safety and viral safety. The annual validated infection rate in the IGIV-C group was 0.18 compared to 0.43 in the IGIV-SD group (p=0.023). Nine patients receiving IGIV-C experienced validated infections, compared to 17 patients in IGIV-SD group (p=0.06). Acute sinusitis (validated plus clinically defined) was less frequent in the IGIV-C group (p=0.012). Presence of bronchiectasis did not affect efficacy. Adverse reactions were similar in frequency and severity in both groups. No evidence of viral transmission was observed. IGIV-C appears to be superior to IGIV-SD in preventing validated sinopulmonary infections, especially acute sinusitis, in patients with PID.

Authors
Roifman, CM; Schroeder, H; Berger, M; Sorensen, R; Ballow, M; Buckley, RH; Gewurz, A; Korenblat, P; Sussman, G; Lemm, G
MLA Citation
Roifman, CM, Schroeder, H, Berger, M, Sorensen, R, Ballow, M, Buckley, RH, Gewurz, A, Korenblat, P, Sussman, G, and Lemm, G. "Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial." Int Immunopharmacol 3.9 (September 2003): 1325-1333.
PMID
12890430
Source
pubmed
Published In
International Immunopharmacology
Volume
3
Issue
9
Publish Date
2003
Start Page
1325
End Page
1333

A clinical attempt to treat JAK3-deficient SCID using retroviral-mediated gene transfer to bone marrow CD34+ cells

Authors
Sorrentino, BP; Lu, TH; Ihle, J; Buckley, RH; Cunningham, JM
MLA Citation
Sorrentino, BP, Lu, TH, Ihle, J, Buckley, RH, and Cunningham, JM. "A clinical attempt to treat JAK3-deficient SCID using retroviral-mediated gene transfer to bone marrow CD34+ cells." May 2003.
Source
wos-lite
Published In
Molecular Therapy
Volume
7
Issue
5
Publish Date
2003
Start Page
S449
End Page
S449

Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%).

BACKGROUND AND OBJECTIVES: A new intravenous immunoglobulin (IGIV) process has been developed that integrates efficient inactivation of enveloped virus, using caprylate, with immunoglobulin G (IgG) purification and caprylate removal by column chromatography. Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV-C, 10% (Gamunex, 10%), formulated with glycine, with the licensed solvent-detergent (SD)-treated intravenous immunoglobulin IGIV-SD, 10% (Gamimune N, 10%), formulated with glycine, and IGIV-C, 5%, formulated with 10% maltose. MATERIALS AND METHODS: Both studies were randomized, multicentre crossover trials of 18 and 20 (respectively) adult patients with primary humoral immune deficiency in which patients received one IGIV product for three consecutive periods (3-4 weeks) before crossing over to the other product. Pharmacokinetic parameters were determined after the third infusion of each product. RESULTS: IGIV-C, 10% was bioequivalent to IGIV-SD, 10%, with half-lives (t1/2) of 35 and 34 days, respectively. IGIV-C, 5%, was bioequivalent to IGIV-C, 10%, with t1/2 of 35 and 36 days, respectively. The products had comparable safety profiles. CONCLUSIONS: The pharmacokinetic profiles observed in these trials indicate that IGIV-C, 10% may replace, and be administered in a manner similar to, IGIV-SD, 10%.

Authors
Ballow, M; Berger, M; Bonilla, FA; Buckley, RH; Cunningham-Rundles, CH; Fireman, P; Kaliner, M; Ochs, HD; Skoda-Smith, S; Sweetser, MT; Taki, H; Lathia, C
MLA Citation
Ballow, M, Berger, M, Bonilla, FA, Buckley, RH, Cunningham-Rundles, CH, Fireman, P, Kaliner, M, Ochs, HD, Skoda-Smith, S, Sweetser, MT, Taki, H, and Lathia, C. "Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%)." Vox Sang 84.3 (April 2003): 202-210.
PMID
12670369
Source
pubmed
Published In
Vox Sanguinis
Volume
84
Issue
3
Publish Date
2003
Start Page
202
End Page
210

T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation.

Transplantation of HLA-identical or haploidentical T cell-depleted allogeneic bone marrow (BM) into SCID infants results in thymus-dependent T cell development in the recipients. Immunoscope analysis of the TCR V beta repertoire was performed on 15 SCID patients given BM transplants. Before and within the first 100 days after bone marrow transplantation (BMT), patients' PBMC displayed an oligoclonal or skewed T cell repertoire, low TCR excision circles (TREC) values, and a predominance of CD45RO(+) T cells. In contrast, the presence of high numbers of CD45RA(+) cells in the circulation of SCID patients >100 days post-BMT correlated with active T cell output by the thymus as revealed by high TREC values and a polyclonal T cell repertoire demonstrated by a Gaussian distribution of V beta-specific peaks. Ten years after BMT, we observed a decrease of the normal polyclonal T cell repertoire and an increase of a more skewed T cell repertoire. A decline of TREC levels and a decrease in the number of CD45RA(+) cells beyond 10 years after BMT was concomitant with the detection of oligoclonal CD3(+)CD8(+)CD45RO(+) cells. The switch from a polyclonal to a more skewed repertoire, observed in the CD3(+)CD8(+)CD45RO(+) T cell subset, is a phenomenon that occurs normally with decreased thymic output during aging, but not as rapidly as in this patient population. We conclude that a normal T cell repertoire develops in SCID patients as a result of thymic output and the repertoire remains highly diverse for the first 10 years after BMT. The TCR diversity positively correlates in these patients with TREC levels.

Authors
Sarzotti, M; Patel, DD; Li, X; Ozaki, DA; Cao, S; Langdon, S; Parrott, RE; Coyne, K; Buckley, RH
MLA Citation
Sarzotti, M, Patel, DD, Li, X, Ozaki, DA, Cao, S, Langdon, S, Parrott, RE, Coyne, K, and Buckley, RH. "T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation." J Immunol 170.5 (March 1, 2003): 2711-2718.
PMID
12594301
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
170
Issue
5
Publish Date
2003
Start Page
2711
End Page
2718

Treatment options for genetically determined immunodeficiency.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Treatment options for genetically determined immunodeficiency." Lancet 361.9357 (February 15, 2003): 541-542.
PMID
12598135
Source
pubmed
Published In
The Lancet
Volume
361
Issue
9357
Publish Date
2003
Start Page
541
End Page
542
DOI
10.1016/S0140-6736(03)12562-7

27. Transplantation immunology: organ and bone marrow.

The discovery of the human MHC in 1967 launched the field of organ and tissue transplantation. More than 800,000 such transplants have been performed during this time. Although matching of donor and recipient for MHC antigens was shown to be of great importance and continues to be so, the development of pharmacologic agents and antilymphocyte antibodies that interfere with the process of graft rejection has had a crucial role in the success of organ transplantation during the past 2 decades. Enormous progress has been made in understanding the immunologic mechanisms of graft rejection and of graft-versus-host disease. The roles of antibodies, antigen-presenting cells, helper and cytotoxic T cells, immune cell surface molecules, and signaling mechanisms and the cytokines they release have been clarified. This understanding is leading to the development of newer immunosuppressive agents targeting various components of the rejection process. Combinations of these agents work synergistically, leading to lower doses and reduced toxicity. Similarly, the development of effective T-cell depletion techniques has been of great importance for bone marrow transplantation when an HLA-identical sibling is not available. The major obstacle to the performance of solid organ transplantation currently is the shortage of donor organs.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "27. Transplantation immunology: organ and bone marrow." J Allergy Clin Immunol 111.2 Suppl (February 2003): S733-S744. (Review)
PMID
12592318
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
111
Issue
2 Suppl
Publish Date
2003
Start Page
S733
End Page
S744

27. Transplantation immunology: Organ and bone marrow

The discovery of the human MHC in 1967 launched the field of organ and tissue transplantation. More than 800,000 such transplants have been performed during this time. Although matching of donor and recipient for MHC antigens was shown to be of great importance and continues to be so, the development of pharmacologic agents and antilymphocyte antibodies that interfere with the process of graft rejection has had a crucial role in the success of organ transplantation during the past 2 decades. Enormous progress has been made in understanding the immunologic mechanisms of graft rejection and of graft-versus-host disease. The roles of antibodies, antigen-presenting cells, helper and cytotoxic T cells, immune cell surface molecules, and signaling mechanisms and the cytokines they release have been clarified. This understanding is leading to the development of newer immunosuppressive agents targeting various components of the rejection process. Combinations of these agents work synergistically, leading to lower doses and reduced toxicity. Similarly, the development of effective T-cell depletion techniques has been of great importance for bone marrow transplantation when an HLA-identical sibling is not available. The major obstacle to the performance of solid organ transplantation currently is the shortage of donor organs.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "27. Transplantation immunology: Organ and bone marrow." Journal of Allergy and Clinical Immunology 111.2 SUPPL. 2 (2003): S733-S744.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
111
Issue
2 SUPPL. 2
Publish Date
2003
Start Page
S733
End Page
S744

Gene therapy for SCID--a complication after remarkable progress.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Gene therapy for SCID--a complication after remarkable progress." Lancet 360.9341 (October 19, 2002): 1185-1186.
PMID
12401240
Source
pubmed
Published In
The Lancet
Volume
360
Issue
9341
Publish Date
2002
Start Page
1185
End Page
1186
DOI
10.1016/S0140-6736(02)11290-6

Immunoglobulin G subclass deficiency: fact or fancy?

Over the past four decades, many patients have been reported to have deficiencies of one or more subclasses of immunoglobulin G (IgG), despite normal total IgG serum concentrations. However, except for those with extremely low or absent IgG2 concentrations and an inability to produce antibodies to polysaccharide antigens, it is difficult to know the true biologic significance of the many reported IgG subclass deficiencies. Completely asymptomatic individuals who totally lack IgG1, IgG2, IgG4, or IgA1 because of heavy-chain gene deletions have been described as producing antibodies normally. In addition, numerous healthy children who have low levels of IgG2 but normal responses to polysaccharide antigens when immunized have been similarly described. From these observations, it can be concluded that IgG subclass measurement is not very helpful in the general assessment of immune function. Such assays provide no information about the patient's capacity to produce specific antibodies to protein, polysaccharide, or viral antigens.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Immunoglobulin G subclass deficiency: fact or fancy?." Curr Allergy Asthma Rep 2.5 (September 2002): 356-360. (Review)
PMID
12165200
Source
pubmed
Published In
Current Allergy and Asthma Reports
Volume
2
Issue
5
Publish Date
2002
Start Page
356
End Page
360

Primary immunodeficiency diseases: dissectors of the immune system.

The past 50 years have seen enormous progress in this field. An unknown concept until 1952, there are now more than 100 different primary immunodeficiency syndromes in the world's literature. Each novel syndrome has shed new insight into the workings of the immune system, dissecting its multiple parts into unique functioning components. This has been especially true over the past decade, as the molecular bases of approximately 40 of these diseases have been identified in rapid succession. Advances in the treatment of these diseases have also been impressive. Antibody replacement has been improved greatly by the development of human immunoglobulin preparations that can be safely administered by the intravenous route, and cytokine and humanized anticytokine therapies are now possible through recombinant technologies. The ability to achieve life-saving immune reconstitution of patients with lethal severe combined immunodeficiency by administering rigorously T-cell-depleted allogeneic related haploidentical bone marrow stem cells has extended this option to virtually all such infants, if diagnosed before untreatable infections develop. Finally, the past 3 years have witnessed the first truly successful gene therapy. The impressive results in X-linked severe combined immunodeficiency offer hope that this approach can be extended to many more diseases in the future.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Primary immunodeficiency diseases: dissectors of the immune system." Immunol Rev 185 (July 2002): 206-219.
PMID
12190932
Source
pubmed
Published In
Immunological Reviews
Volume
185
Publish Date
2002
Start Page
206
End Page
219

Primary cellular immunodeficiencies.

Genetic defects in T-cell function lead to susceptibility to infections or to other clinical problems that are more grave than those seen in disorders resulting in antibody deficiency alone. Those affected usually present during infancy with either common or opportunistic infections and rarely survive beyond infancy or childhood. The spectrum of T-cell defects ranges from the syndrome of severe combined immunodeficiency, in which T-cell function is absent, to combined immunodeficiency disorders in which there is some, but not adequate, T-cell function for a normal life span. Recent discoveries of the molecular causes of many of these defects have led to a new understanding of the flawed biology underlying the ever-growing number of defects. Most of these conditions could be diagnosed by means of screening for lymphopenia or for T-cell deficiency in cord blood at birth. Early recognition of those so afflicted is essential to the application of the most appropriate treatments for these conditions at a very early age. The latter treatments include both transplantation and gene therapy in addition to immunoglobulin replacement. Fully defining the molecular defects of such patients is also essential for genetic counseling of family members and prenatal diagnosis.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Primary cellular immunodeficiencies." J Allergy Clin Immunol 109.5 (May 2002): 747-757. (Review)
PMID
11994695
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
109
Issue
5
Publish Date
2002
Start Page
747
End Page
757

T cell repertoire diversity after hematopoietic stem cell transplantation in SCID patients.

Authors
Sarzotti, M; Patel, DD; Li, X; Cao, S; Ozaki, D; Langdon, S; Parrott, RE; Coyne, K; Buckley, RH
MLA Citation
Sarzotti, M, Patel, DD, Li, X, Cao, S, Ozaki, D, Langdon, S, Parrott, RE, Coyne, K, and Buckley, RH. "T cell repertoire diversity after hematopoietic stem cell transplantation in SCID patients." FASEB JOURNAL 16.5 (March 22, 2002): A1030-A1030.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
5
Publish Date
2002
Start Page
A1030
End Page
A1030

Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival.

All genetic types of severe combined immunodeficiency (SCID) can be cured by stem cell transplantation from related donors. The survival rate approaches 80%, and most deaths result from opportunistic infections acquired before transplantation. It was hypothesized that the survival rate and kinetics of immune reconstitution would be improved for infants receiving transplants in the neonatal period (first 28 days of life), prior to the development of infections. A 19.2-year retrospective/prospective analysis compared immune function in 21 SCID infants receiving transplants in the neonatal period with that in 70 SCID infants receiving transplants later. Lymphocyte phenotypes, proliferative responses to mitogens, immunoglobulin levels, and T-cell antigen receptor excision circles (TRECs) were measured before transplantation and sequentially after transplantation. Of 21 SCID infants with transplantations in the neonatal period, 20 (95%) survive. Neonates were lymphopenic at birth (1118 +/- 128 lymphocytes per cubic millimeter). Infants receiving transplants early developed higher lymphocyte responses to phytohemagglutinin and higher numbers of CD3(+) and CD45RA(+) T cells in the first 3 years of life than those receiving transplants late (P <.05). TRECs peaked earlier and with higher values (P <.01) in the neonatal transplantations (181 days to 1 year) than in the late transplantations (1 to 3 years). SCID recipients of allogeneic, related hematopoietic stem cells in the neonatal period had higher levels of T-cell reconstitution and thymic output and a higher survival rate than those receiving transplants after 28 days of life. An improved outcome for this otherwise fatal syndrome could be achieved with newborn screening for lymphopenia so that transplantation could be performed under favorable thymopoietic conditions.

Authors
Myers, LA; Patel, DD; Puck, JM; Buckley, RH
MLA Citation
Myers, LA, Patel, DD, Puck, JM, and Buckley, RH. "Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival." Blood 99.3 (February 1, 2002): 872-878.
PMID
11806989
Source
pubmed
Published In
Blood
Volume
99
Issue
3
Publish Date
2002
Start Page
872
End Page
878

American Pediatric Society Presidential Address 2000: reflections on the 20th and 21st centuries.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "American Pediatric Society Presidential Address 2000: reflections on the 20th and 21st centuries." Pediatr Res 51.1 (January 2002): 119-123.
PMID
11756650
Source
pubmed
Published In
Pediatric Research
Volume
51
Issue
1
Publish Date
2002
Start Page
119
End Page
123
DOI
10.1203/00006450-200201000-00021

Distinctive clinical and laboratory features of autosomal-recessive hyperIgM syndrome

Authors
Shaw, SG; Buckley, RH; Roberts, J
MLA Citation
Shaw, SG, Buckley, RH, and Roberts, J. "Distinctive clinical and laboratory features of autosomal-recessive hyperIgM syndrome." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 109.1 (January 2002): S254-S254.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
109
Issue
1
Publish Date
2002
Start Page
S254
End Page
S254
DOI
10.1016/S0091-6749(02)81911-X

Prevalence of X-linked lymphoproliferative (XLP) disease mutation among male patients with CVID

Authors
Mustillo, PJ; Coyne, KE; Roberts, J; Nichols, K; Buckley, RH
MLA Citation
Mustillo, PJ, Coyne, KE, Roberts, J, Nichols, K, and Buckley, RH. "Prevalence of X-linked lymphoproliferative (XLP) disease mutation among male patients with CVID." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 109.1 (January 2002): S276-S276.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
109
Issue
1
Publish Date
2002
Start Page
S276
End Page
S276
DOI
10.1016/S0091-6749(02)81977-7

Natural killer (NK) cell ontogeny in severe combined immunodeficiency (SCID) after bone marrow transplantation (BMT)

Authors
Piltch, RG; Parrott, R; Buckley, RH
MLA Citation
Piltch, RG, Parrott, R, and Buckley, RH. "Natural killer (NK) cell ontogeny in severe combined immunodeficiency (SCID) after bone marrow transplantation (BMT)." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 109.1 (January 2002): S277-S277.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
109
Issue
1
Publish Date
2002
Start Page
S277
End Page
S277
DOI
10.1016/S0091-6749(02)81980-7

Patients with atypical X-linked severe combined immunodeficiency (XSCID) may benefit from hematopoietic stem cell gene therapy.

Authors
Puck, JM; Hay, BN; Hsu, AP; Fischer, R; Tsai, E; Uzel, G; Buckley, RH; Malech, HL
MLA Citation
Puck, JM, Hay, BN, Hsu, AP, Fischer, R, Tsai, E, Uzel, G, Buckley, RH, and Malech, HL. "Patients with atypical X-linked severe combined immunodeficiency (XSCID) may benefit from hematopoietic stem cell gene therapy." BLOOD CELLS MOLECULES AND DISEASES 28.3 (2002): 343-343.
Source
wos-lite
Published In
Blood Cells, Molecules and Diseases
Volume
28
Issue
3
Publish Date
2002
Start Page
343
End Page
343

Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases.

Janus kinases comprise carboxyterminal kinase, pseudokinase, SH2-like, and N-terminal FERM domains. We identified three patient-derived mutations in the FERM domain of Jak3 and investigated the functional consequences of these mutations. These mutations inhibited receptor binding and also abrogated kinase activity, suggesting interactions between the FERM and kinase domains. In fact, the domains were found to physically associate, and coexpression of the FERM domain enhanced activity of the isolated kinase domain. Conversely, staurosporine, which alters kinase domain structure, disrupted receptor binding, even though the catalytic activity of Jak3 is dispensable for receptor binding. Thus, the Jak FERM domain appears to have two critical functions: receptor interaction and maintenance of kinase integrity.

Authors
Zhou, YJ; Chen, M; Cusack, NA; Kimmel, LH; Magnuson, KS; Boyd, JG; Lin, W; Roberts, JL; Lengi, A; Buckley, RH; Geahlen, RL; Candotti, F; Gadina, M; Changelian, PS; O'Shea, JJ
MLA Citation
Zhou, YJ, Chen, M, Cusack, NA, Kimmel, LH, Magnuson, KS, Boyd, JG, Lin, W, Roberts, JL, Lengi, A, Buckley, RH, Geahlen, RL, Candotti, F, Gadina, M, Changelian, PS, and O'Shea, JJ. "Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases." Mol Cell 8.5 (November 2001): 959-969.
PMID
11741532
Source
pubmed
Published In
Molecular Cell
Volume
8
Issue
5
Publish Date
2001
Start Page
959
End Page
969

Alterations of the X-linked lymphoproliferative disease gene SH2D1A in common variable immunodeficiency syndrome.

X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency caused by a defect in the SH2D1A gene. At least 3 major manifestations characterize its clinical presentation: fatal infectious mononucleosis (FIM), lymphomas, and immunoglobulin deficiencies. Common variable immunodeficiency (CVID) is a syndrome characterized by immunoglobulin deficiency leading to susceptibility to infection. In some patients with CVID, a defective btk or CD40-L gene has been found, but most often there is no clearly identified etiology. Here, 2 unrelated families in whom male members were affected by CVID were examined for a defect in the XLP gene. In one family previously reported in the literature as having progressive immunoglobulin deficiencies, 3 brothers were examined for recurrent respiratory infections, whereas female family members showed only elevated serum immunoglobulin A levels. A grandson of one of the brothers died of a severe Aspergillus infection secondary to progressive immunoglobulin deficiency, FIM, aplastic anemia, and B-cell lymphoma. In the second family, 2 brothers had B lymphocytopenia and immunoglobulin deficiencies. X-linked agammaglobulinemia syndrome was excluded genetically, and they were classified as having CVID. The occurrence of FIM in a male cousin of the brothers led to the XLP diagnosis. Because the SH2D1A gene was found altered in both families, these findings indicate that XLP must be considered when more than one male patient with CVID is encountered in the same family, and SH2D1A must be analyzed in all male patients with CVID. Moreover, these data link defects in the SH2D1A gene to abnormal B-lymphocyte development and to dysgammaglobulinemia in female members of families with XLP disease.

Authors
Morra, M; Silander, O; Calpe, S; Choi, M; Oettgen, H; Myers, L; Etzioni, A; Buckley, R; Terhorst, C
MLA Citation
Morra, M, Silander, O, Calpe, S, Choi, M, Oettgen, H, Myers, L, Etzioni, A, Buckley, R, and Terhorst, C. "Alterations of the X-linked lymphoproliferative disease gene SH2D1A in common variable immunodeficiency syndrome." Blood 98.5 (September 1, 2001): 1321-1325.
PMID
11520777
Source
pubmed
Published In
Blood
Volume
98
Issue
5
Publish Date
2001
Start Page
1321
End Page
1325

Primary immunodeficiency disorders in pediatric patients: clinical features and imaging findings.

Authors
Yin, EZ; Frush, DP; Donnelly, LF; Buckley, RH
MLA Citation
Yin, EZ, Frush, DP, Donnelly, LF, and Buckley, RH. "Primary immunodeficiency disorders in pediatric patients: clinical features and imaging findings." AJR Am J Roentgenol 176.6 (June 2001): 1541-1552. (Review)
PMID
11373230
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
176
Issue
6
Publish Date
2001
Start Page
1541
End Page
1552
DOI
10.2214/ajr.176.6.1761541

Cutaneous complications of BCG vaccination in infants with immune disorders: two cases and a review of the literature.

Two infants, one with a T-cell-signaling defect resulting in a primary immunodeficiency syndrome and the other with severe combined immunodeficiency (SCID), are described. Both infants developed cutaneous infections secondary to their bacillus Calmette-Guérin (BCG) vaccinations. Both patients were from countries where BCG is routinely administered in infancy. The infant with the T-cell-signaling defect developed a disseminated infection involving the skin, while the infant with SCID developed a localized cutaneous infection at the site of his BCG immunization. These two cases resemble other reported cases of cutaneous BCG infection following routine vaccination in immunocompromised patients. Mycobacterium bovis infection should be considered in patients with cutaneous eruptions who have received BCG vaccination, especially those who are immunocompromised.

Authors
Antaya, RJ; Gardner, ES; Bettencourt, MS; Daines, M; Denise, Y; Uthaisangsook, S; Buckley, RH; Prose, NS
MLA Citation
Antaya, RJ, Gardner, ES, Bettencourt, MS, Daines, M, Denise, Y, Uthaisangsook, S, Buckley, RH, and Prose, NS. "Cutaneous complications of BCG vaccination in infants with immune disorders: two cases and a review of the literature." Pediatr Dermatol 18.3 (May 2001): 205-209. (Review)
PMID
11437999
Source
pubmed
Published In
Pediatric Dermatology
Volume
18
Issue
3
Publish Date
2001
Start Page
205
End Page
209

The hyper-IgE syndrome.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The hyper-IgE syndrome." Clin Rev Allergy Immunol 20.1 (February 2001): 139-154. (Review)
PMID
11269224
Source
pubmed
Published In
Clinical Reviews in Allergy & Immunology
Volume
20
Issue
1
Publish Date
2001
Start Page
139
End Page
154
DOI
10.1385/CRIAI:20:1:139

Adenosine deaminase (ADA) deficiency, multiple phenotypes

Authors
Koleilat, MA; Buckley, RH; Loubser, M
MLA Citation
Koleilat, MA, Buckley, RH, and Loubser, M. "Adenosine deaminase (ADA) deficiency, multiple phenotypes." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 107.2 (February 2001): S202-S202.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
107
Issue
2
Publish Date
2001
Start Page
S202
End Page
S202

Pharmacokinetics of a novel, intravenous immunoglobulin preparation

Authors
Ballow, M; Berger, M; Bonilla, FA; Buckley, RH; Cunningham-Rundles, C; Fireman, P; Kaliner, M; Ochs, H; Skoda-Smith, S; Sweetser, M; Taki, H; Lathia, C
MLA Citation
Ballow, M, Berger, M, Bonilla, FA, Buckley, RH, Cunningham-Rundles, C, Fireman, P, Kaliner, M, Ochs, H, Skoda-Smith, S, Sweetser, M, Taki, H, and Lathia, C. "Pharmacokinetics of a novel, intravenous immunoglobulin preparation." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 107.2 (February 2001): S208-S208.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
107
Issue
2
Publish Date
2001
Start Page
S208
End Page
S208

CD27+memory B cells in human severe combined immunodeficiency (SCID)

Authors
Buckley, RH; Parrott, RE
MLA Citation
Buckley, RH, and Parrott, RE. "CD27+memory B cells in human severe combined immunodeficiency (SCID)." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 107.2 (February 2001): S137-S137.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
107
Issue
2
Publish Date
2001
Start Page
S137
End Page
S137

Intestinal lymphangiectasia masquerading as severe combined immunodeficiency (SCID)

Authors
Shaw, SG; Ahmed, A; Treem, WR; Buckley, RH
MLA Citation
Shaw, SG, Ahmed, A, Treem, WR, and Buckley, RH. "Intestinal lymphangiectasia masquerading as severe combined immunodeficiency (SCID)." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 107.2 (February 2001): S201-S201.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
107
Issue
2
Publish Date
2001
Start Page
S201
End Page
S201

Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome.

Recent studies have shown that mutations in a newly described RNA editing enzyme, activation-induced cytidine deaminase (AID), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency of mutations in AID, we evaluated a group of 27 patients with hyper IgM syndrome who did not have defects in CD40 ligand and 23 patients with common variable immunodeficiency. Three different mutations in AID were identified in 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lumbee Indians, and a brother and sister from Okinawa. No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM syndrome, the patients with mutations in AID were older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID.

Authors
Minegishi, Y; Lavoie, A; Cunningham-Rundles, C; Bédard, PM; Hébert, J; Côté, L; Dan, K; Sedlak, D; Buckley, RH; Fischer, A; Durandy, A; Conley, ME
MLA Citation
Minegishi, Y, Lavoie, A, Cunningham-Rundles, C, Bédard, PM, Hébert, J, Côté, L, Dan, K, Sedlak, D, Buckley, RH, Fischer, A, Durandy, A, and Conley, ME. "Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome." Clin Immunol 97.3 (December 2000): 203-210.
PMID
11112359
Source
pubmed
Published In
Clinical Immunology
Volume
97
Issue
3
Publish Date
2000
Start Page
203
End Page
210
DOI
10.1006/clim.2000.4956

Primary immunodeficiency diseases due to defects in lymphocytes.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Primary immunodeficiency diseases due to defects in lymphocytes." N Engl J Med 343.18 (November 2, 2000): 1313-1324. (Review)
PMID
11058677
Source
pubmed
Published In
The New England journal of medicine
Volume
343
Issue
18
Publish Date
2000
Start Page
1313
End Page
1324
DOI
10.1056/NEJM200011023431806

Unusual X-linked SCID phenotype due to mutation of the poly-A addition signal of IL2RG.

Authors
Hsu, AP; Tsai, EJ; Anderson, SM; Fischer, RE; Malech, H; Buckley, RH; Puck, JM
MLA Citation
Hsu, AP, Tsai, EJ, Anderson, SM, Fischer, RE, Malech, H, Buckley, RH, and Puck, JM. "Unusual X-linked SCID phenotype due to mutation of the poly-A addition signal of IL2RG." AMERICAN JOURNAL OF HUMAN GENETICS 67.4 (October 2000): 50-50.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
67
Issue
4
Publish Date
2000
Start Page
50
End Page
50

Gene therapy for human SCID: dreams become reality.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Gene therapy for human SCID: dreams become reality." Nat Med 6.6 (June 2000): 623-624.
PMID
10835669
Source
pubmed
Published In
Nature Medicine
Volume
6
Issue
6
Publish Date
2000
Start Page
623
End Page
624
DOI
10.1038/76185

Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency.

BACKGROUND: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cell-depleted marrow stem cells from haploidentical donors, with whom there is a single haplotype mismatch, without the need for chemotherapy before transplantation or prophylaxis against graft-versus-host disease. The role of the thymus in this process is unknown. METHODS: We analyzed the phenotypes of circulating T cells and the proliferative responses of peripheral-blood mononuclear cells to phytohemagglutinin in 83 patients with severe combined immunodeficiency who received allogeneic marrow transplants without T-cell ablation from related donors over an 18-year period. We also tested for the presence of episomes of T-cell antigen receptors (extrachromosomal DNA circles formed during intrathymic T-cell development) to assess thymus-dependent T-cell reconstitution. RESULTS: Before and early after transplantation, the numbers of circulating T cells were low, with a predominance of mature CD45RO+ T cells (primarily resulting from the transplacental transfer of maternal cells); T-cell antigen-receptor episomes were undetectable in peripheral-blood mononuclear cells. In 73 of the infants, thymus-derived T cells expressing CD45RA and T-cell antigen-receptor episomes were detected within three to six weeks after transplantation. The mean (+/-SD) value for thymus-dependent T-cell antigen-receptor episomes peaked (at 7311+/-8652 per microgram of peripheral-blood mononuclear-cell DNA) 1 to 2 years after transplantation and declined to low levels (less than 100 episomes per microgram of DNA) within 14 years, as compared with a gradual decline from birth to the age of about 80 years in normal subjects. CONCLUSIONS: The vestigial thymus in infants with severe combined immunodeficiency is functional and can produce enough T cells after bone marrow transplantation to provide normal immune function.

Authors
Patel, DD; Gooding, ME; Parrott, RE; Curtis, KM; Haynes, BF; Buckley, RH
MLA Citation
Patel, DD, Gooding, ME, Parrott, RE, Curtis, KM, Haynes, BF, and Buckley, RH. "Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency." N Engl J Med 342.18 (May 4, 2000): 1325-1332.
PMID
10793165
Source
pubmed
Published In
The New England journal of medicine
Volume
342
Issue
18
Publish Date
2000
Start Page
1325
End Page
1332
DOI
10.1056/NEJM200005043421804

Chronic granulomatous disease. Report on a national registry of 368 patients.

A registry of United States residents with chronic granulomatous disease (CGD) was established in 1993 in order to estimate the minimum incidence of this uncommon primary immunodeficiency disease and characterize its epidemiologic and clinical features. To date, 368 patients have been registered; 259 have the X-linked recessive form of CGD, 81 have 1 of the autosomal recessive forms, and in 28 the mode of inheritance is unknown. The minimum estimate of birth rate is between 1/200,000 and 1/250,000 live births for the period 1980-1989. Pneumonia was the most prevalent infection (79% of patients; Aspergillus most prevalent cause), followed by suppurative adenitis (53% of patients; Staphylococcus most prevalent cause), subcutaneous abscess (42% of patients; Staphylococcus most prevalent cause), liver abscess (27% of patients; Staphylococcus most prevalent cause), osteomyelitis (25% of patients; Serratia most prevalent cause), and sepsis (18% of patients; Salmonella most prevalent cause). Fifteen percent of patients had gastric outlet obstruction, 10% urinary tract obstruction, and 17% colitis/enteritis. Ten percent of X-linked recessive kindreds and 3% of autosomal recessive kindreds had family members with lupus. Eighteen percent of patients either were deceased when registered or died after being registered. The most common causes of death were pneumonia and/or sepsis due to Aspergillus (23 patients) or Burkholderia cepacia (12 patients). Patients with the X-linked recessive form of the disease appear to have a more serious clinical phenotype than patients with the autosomal recessive forms of the disease, based on the fact that they are diagnosed significantly earlier (mean, 3.01 years of age versus 7.81 years of age, respectively), have a significantly higher prevalence of perirectal abscess (17% versus 7%), suppurative adenitis (59% versus 32%), bacteremia/fungemia (21% versus 10%), gastric obstruction (19% versus 5%), and urinary tract obstruction (11% versus 3%), and a higher mortality (21.2% versus 8.6%).

Authors
Winkelstein, JA; Marino, MC; Johnston, RB; Boyle, J; Curnutte, J; Gallin, JI; Malech, HL; Holland, SM; Ochs, H; Quie, P; Buckley, RH; Foster, CB; Chanock, SJ; Dickler, H
MLA Citation
Winkelstein, JA, Marino, MC, Johnston, RB, Boyle, J, Curnutte, J, Gallin, JI, Malech, HL, Holland, SM, Ochs, H, Quie, P, Buckley, RH, Foster, CB, Chanock, SJ, and Dickler, H. "Chronic granulomatous disease. Report on a national registry of 368 patients." Medicine (Baltimore) 79.3 (May 2000): 155-169.
PMID
10844935
Source
pubmed
Published In
Medicine
Volume
79
Issue
3
Publish Date
2000
Start Page
155
End Page
169

Correction of complete IFNGR2 deficiency with transplantation of bone marrow from a parent

Authors
Shaw, SG; Dorman, SE; Uzel, G; Holland, SM; Buckley, RH
MLA Citation
Shaw, SG, Dorman, SE, Uzel, G, Holland, SM, and Buckley, RH. "Correction of complete IFNGR2 deficiency with transplantation of bone marrow from a parent." FASEB JOURNAL 14.6 (April 20, 2000): A933-A933.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
14
Issue
6
Publish Date
2000
Start Page
A933
End Page
A933

Haploidentical T cell-depleted bone marrow transplantation into a premature infant with X-linked severe combined immunodeficiency (X-SCID)

Authors
Shaw, S; Buckley, RH
MLA Citation
Shaw, S, and Buckley, RH. "Haploidentical T cell-depleted bone marrow transplantation into a premature infant with X-linked severe combined immunodeficiency (X-SCID)." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 105.1 (January 2000): S266-S266.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
105
Issue
1
Publish Date
2000
Start Page
S266
End Page
S266
DOI
10.1016/S0091-6749(00)91216-8

Thymic output after non-ablative allogeneic hematopoietic stem cell transplantation in infants with severe combined immunodeficiency (SCID)

Authors
Patel, D; Gooding, M; Parrott, R; Curtis, K; Haynes, B; Buckley, RH
MLA Citation
Patel, D, Gooding, M, Parrott, R, Curtis, K, Haynes, B, and Buckley, RH. "Thymic output after non-ablative allogeneic hematopoietic stem cell transplantation in infants with severe combined immunodeficiency (SCID)." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 105.1 (January 2000): S264-S265.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
105
Issue
1
Publish Date
2000
Start Page
S264
End Page
S265
DOI
10.1016/S0091-6749(00)91212-0

Successful and rapid immune reconstitution using a pregnant donor for T-Cell depleted haploidentical bone marrow transplantation for a patient with severe combined immunodeficiency

Authors
Lowe, D; Livingston, E; Penning, D; Buckley, RH
MLA Citation
Lowe, D, Livingston, E, Penning, D, and Buckley, RH. "Successful and rapid immune reconstitution using a pregnant donor for T-Cell depleted haploidentical bone marrow transplantation for a patient with severe combined immunodeficiency." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 105.1 (January 2000): S266-S266.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
105
Issue
1
Publish Date
2000
Start Page
S266
End Page
S266
DOI
10.1016/S0091-6749(00)91215-6

Advances in the understanding and treatment of human severe combined immunodeficiency.

Human severe combined immunodeficiency (SCID) can result from mutations in any one of at least seven different genes, including those for adenosine deaminase, the common cytokine receptor gamma chain, Janus kinase 3, IL-7 receptor alpha chain, recombinase activation genes 1 and 2, and CD45. Except for adenosine deaminase, knowledge concerning the latter causes of human SCID has accrued since 1993. Advances in the treatment of this syndrome have been no less significant. Since 1982 it has been possible, by rigorous depletion of T cells from the donor marrow, to use related marrow donors other than HLA-identical siblings for successful treatment of infants with this condition. The success rate with the latter type of transplant exceeds 95% if a transplant can be performed within the first 3.5 mo of life, making early diagnosis crucial. Recently, gene therapy has also been successful in infants with X-linked SCID.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Advances in the understanding and treatment of human severe combined immunodeficiency." Immunol Res 22.2-3 (2000): 237-251. (Review)
PMID
11339359
Source
pubmed
Published In
Immunologic Research
Volume
22
Issue
2-3
Publish Date
2000
Start Page
237
End Page
251
DOI
10.1385/IR:22:2-3:237

Transplantation of thymus tissue in complete DiGeorge syndrome.

BACKGROUND: The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function. METHODS: We treated five infants (age, one to four months) with complete DiGeorge syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell-receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell-receptor genes. RESULTS: After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the surviving patients showed normal morphologic features and active T-cell production. In three patients, donor T cells could be detected about four weeks after transplantation, although there was no evidence of graft-versus-host disease on biopsy or at autopsy. In one patient, the T-cell development within the graft was demonstrated to accompany the appearance of recently developed T cells in the periphery and coincided with the onset of normal T-cell function. In one patient, there was evidence of thymus function and CD45RA+CD62L+ T cells more than five years after transplantation. CONCLUSIONS: In some infants with profound immunodeficiency and complete DiGeorge syndrome, the transplantation of thymus tissue can restore normal immune function. Early thymus transplantation - before the development of infectious complications - may promote successful immune reconstitution.

Authors
Markert, ML; Boeck, A; Hale, LP; Kloster, AL; McLaughlin, TM; Batchvarova, MN; Douek, DC; Koup, RA; Kostyu, DD; Ward, FE; Rice, HE; Mahaffey, SM; Schiff, SE; Buckley, RH; Haynes, BF
MLA Citation
Markert, ML, Boeck, A, Hale, LP, Kloster, AL, McLaughlin, TM, Batchvarova, MN, Douek, DC, Koup, RA, Kostyu, DD, Ward, FE, Rice, HE, Mahaffey, SM, Schiff, SE, Buckley, RH, and Haynes, BF. "Transplantation of thymus tissue in complete DiGeorge syndrome." N Engl J Med 341.16 (October 14, 1999): 1180-1189.
PMID
10523153
Source
pubmed
Published In
The New England journal of medicine
Volume
341
Issue
16
Publish Date
1999
Start Page
1180
End Page
1189
DOI
10.1056/NEJM199910143411603

Genetic linkage of hyper-IgE syndrome to chromosome 4.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as an autosomal dominant trait with variable expressivity. Nineteen kindreds with multiple cases of HIES were scored for clinical and laboratory findings and were genotyped with polymorphic markers in a candidate region on human chromosome 4. Linkage analysis showed a maximum two-point LOD score of 3.61 at recombination fraction of 0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES.

Authors
Grimbacher, B; Schäffer, AA; Holland, SM; Davis, J; Gallin, JI; Malech, HL; Atkinson, TP; Belohradsky, BH; Buckley, RH; Cossu, F; Español, T; Garty, BZ; Matamoros, N; Myers, LA; Nelson, RP; Ochs, HD; Renner, ED; Wellinghausen, N; Puck, JM
MLA Citation
Grimbacher, B, Schäffer, AA, Holland, SM, Davis, J, Gallin, JI, Malech, HL, Atkinson, TP, Belohradsky, BH, Buckley, RH, Cossu, F, Español, T, Garty, BZ, Matamoros, N, Myers, LA, Nelson, RP, Ochs, HD, Renner, ED, Wellinghausen, N, and Puck, JM. "Genetic linkage of hyper-IgE syndrome to chromosome 4." Am J Hum Genet 65.3 (September 1999): 735-744.
PMID
10441580
Source
pubmed
Published In
The American Journal of Human Genetics
Volume
65
Issue
3
Publish Date
1999
Start Page
735
End Page
744
DOI
10.1086/302547

Treatment of severe combined immunodeficiency - Reply

Authors
Buckley, RH; Myers, LA
MLA Citation
Buckley, RH, and Myers, LA. "Treatment of severe combined immunodeficiency - Reply." NEW ENGLAND JOURNAL OF MEDICINE 341.4 (July 22, 1999): 291-292.
Source
wos-lite
Published In
The New England journal of medicine
Volume
341
Issue
4
Publish Date
1999
Start Page
291
End Page
292

Deficiency of nuclear factor of activated T cells 1(NFAT1) in combined immunodeficiencies.

Authors
Daines, MO; Roberts, JL; Buckley, RH
MLA Citation
Daines, MO, Roberts, JL, and Buckley, RH. "Deficiency of nuclear factor of activated T cells 1(NFAT1) in combined immunodeficiencies." FASEB JOURNAL 13.4 (March 12, 1999): A642-A642.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
13
Issue
4
Publish Date
1999
Start Page
A642
End Page
A642

Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency.

BACKGROUND: Since 1968 it has been known that bone marrow transplantation can ameliorate severe combined immunodeficiency, but data on the long-term efficacy of this treatment are limited. We prospectively studied immunologic function in 89 consecutive infants with severe combined immunodeficiency who received hematopoietic stem-cell transplants at Duke University Medical Center between May 1982 and September 1998. METHODS: Serum immunoglobulin levels and lymphocyte phenotypes and function were assessed and genetic analyses performed according to standard methods. Bone marrow was depleted of T cells by agglutination with soybean lectin and by sheep-erythrocyte rosetting before transplantation. RESULTS: Seventy-seven of the infants received T-cell-depleted, HLA-haploidentical parental marrow, and 12 received HLA-identical marrow from a related donor; 3 of the recipients of haploidentical marrow also received placental-blood transplants from unrelated donors. Except for two patients who received placental blood, none of the recipients received chemotherapy before transplantation or prophylaxis against graft-versus-host disease. Of the 89 infants, 72 (81 percent) were still alive 3 months to 16.5 years after transplantation, including all of the 12 who received HLA-identical marrow, 60 of the 77 (78 percent) who were given haploidentical marrow, and 2 of the 3 (67 percent) who received both haploidentical marrow and placental blood. T-cell function became normal within two weeks after transplantation in the patients who received unfractionated HLA-identical marrow but usually not until three to four months after transplantation in those who received T-cell-depleted marrow. At the time of the most recent evaluation, all but 4 of the 72 survivors had normal T-cell function, and all the T cells in their blood were of donor origin. B-cell function remained abnormal in many of the recipients of haploidentical marrow. In 26 children (5 recipients of HLA-identical marrow and 21 recipients of haploidentical marrow) between 2 percent and 100 percent of B cells were of donor origin. Forty-five of the 72 children were receiving intravenous immune globulin. CONCLUSIONS: Transplantation of marrow from a related donor is a life-saving and life-sustaining treatment for patients with any type of severe combined immunodeficiency, even when there is no HLA-identical donor.

Authors
Buckley, RH; Schiff, SE; Schiff, RI; Markert, L; Williams, LW; Roberts, JL; Myers, LA; Ward, FE
MLA Citation
Buckley, RH, Schiff, SE, Schiff, RI, Markert, L, Williams, LW, Roberts, JL, Myers, LA, and Ward, FE. "Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency." N Engl J Med 340.7 (February 18, 1999): 508-516.
PMID
10021471
Source
pubmed
Published In
The New England journal of medicine
Volume
340
Issue
7
Publish Date
1999
Start Page
508
End Page
516
DOI
10.1056/NEJM199902183400703

Clinical and immunologic spectrum of the hyper IgM syndrome.

Authors
Uthaisangsook, S; Buckley, RH
MLA Citation
Uthaisangsook, S, and Buckley, RH. "Clinical and immunologic spectrum of the hyper IgM syndrome." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 103.1 (January 1999): S148-S149.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
103
Issue
1
Publish Date
1999
Start Page
S148
End Page
S149

Successful HLA-identical bone marrow transplantation in combined immunodeficiency without pre-transplant chemoablation or GVHD prophylaxis.

Authors
Riester, DE; Myers, LA; Buckley, RH
MLA Citation
Riester, DE, Myers, LA, and Buckley, RH. "Successful HLA-identical bone marrow transplantation in combined immunodeficiency without pre-transplant chemoablation or GVHD prophylaxis." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 103.1 (January 1999): S118-S118.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
103
Issue
1
Publish Date
1999
Start Page
S118
End Page
S118

Deficiency of nuclear factor of activated T cells 1 (NFAT1) in combined immunodeficiencies.

Authors
Daines, MO; Roberts, JL; Buckley, RH
MLA Citation
Daines, MO, Roberts, JL, and Buckley, RH. "Deficiency of nuclear factor of activated T cells 1 (NFAT1) in combined immunodeficiencies." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 103.1 (January 1999): S118-S118.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
103
Issue
1
Publish Date
1999
Start Page
S118
End Page
S118

Treatment of severe combined immunodeficiency [5] (multiple letters)

Authors
Flake, AW; Zanjani, ED; Buckley, RH; Myers, LA
MLA Citation
Flake, AW, Zanjani, ED, Buckley, RH, and Myers, LA. "Treatment of severe combined immunodeficiency [5] (multiple letters)." New England Journal of Medicine 341.4 (1999): 291-292.
PMID
10419393
Source
scival
Published In
The New England journal of medicine
Volume
341
Issue
4
Publish Date
1999
Start Page
291
End Page
292
DOI
10.1056/NEJM199907223410416

Cellular therapy for severe combined immunodeficiency: Transplant options and impact of donor type and graft manipulation on long-term graft function and completeness of immune reconstitution

While the ideal donor of stem cells for an infant with severe combined immunodeficiency (SCID) is an HLA-identical sibling, one of the most important therapeutic advances for this condition over the past two decades has been the development of effective methods to deplete post-thymic T cells from haploidentical parental bone marrow. There is extensive experience now showing that the remaining stem cells will confer immunity on infants with SCID without the necessity for pre-transplant conditioning or post-transplant graft-versus-host disease prophylaxis. T cell function was present as soon as 2 weeks after unfractionated marrow but not until 3-4 months after T cell depleted haploidentical marrow stem cells. A total of 580 transplanted SCID patients were identified by the author in a worldwide survey and 375 (65%) were surviving, including 77 transplanted at the author's institution, of whom 60 (78%) were surviving). One hundred twenty-five SCIDs had received HLA-identical marrow and 105 (84%) were surviving, including 12 of 12 (100%) at the author's institution. Four hundred twenty-one had received haploidentical marrow and 256 (61%) were surviving, including 48/65 or 74% of those performed at the author's institution, and two transplanted in utero elsewhere with T cell-depleted paternal marrow. Experience with matched unrelated adult marrow transplantation in SCID is limited, but 12 of 17 recipients (71%) worldwide were surviving. Two of three SCID infants given cord blood transplants at the author's institution were surviving.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Cellular therapy for severe combined immunodeficiency: Transplant options and impact of donor type and graft manipulation on long-term graft function and completeness of immune reconstitution." Cancer Research Therapy and Control 9.1-2 (1999): 73-79.
Source
scival
Published In
Cancer Research, Therapy and Control
Volume
9
Issue
1-2
Publish Date
1999
Start Page
73
End Page
79

Angelman syndrome: are the estimates too low?

More than 300 cases of Angelman Syndrome (AS) have been reported. AS is still considered a clinical diagnosis because only approximately 80% of those individuals who meet the clinical criteria will have a maternal deletion of chromosome 15q11-13. Of the reported cases of AS, very few are of adults with AS. We present our findings on 11 adults with AS identified in a long-term residential care facility for persons with severe developmental disabilities. The diagnosis of AS was not recognized at the time of their admission but was established as part of our evaluation. Thus, there may be an underestimate of the true incidence of AS especially in adults with severe developmental disabilities.

Authors
Buckley, RH; Dinno, N; Weber, P
MLA Citation
Buckley, RH, Dinno, N, and Weber, P. "Angelman syndrome: are the estimates too low?." Am J Med Genet 80.4 (December 4, 1998): 385-390.
PMID
9856568
Source
pubmed
Published In
American Journal of Medical Genetics Part A
Volume
80
Issue
4
Publish Date
1998
Start Page
385
End Page
390

Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref. 4), which encodes the common cytokine receptor gamma chain (gamma(c)) that is shared by the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal (T(-)B(+)NK(-)SCID). Some SCID patients lack T cells but retain NK cells. Given diminished T-cell development in Il7- or Il7r-deficient mice and that Il/7r-deficient mice have NK cells, we hypothesized that T(-)B(+)NK(+) SCID might result from defective IL-7 signalling, although apparent differences in the role of the IL-7/IL-7R pathway in humans and mice in T-cell and B-cell development have been suggested. We now demonstrate that defective IL7R expression causes T(-)B(+)NK(+) SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling.

Authors
Puel, A; Ziegler, SF; Buckley, RH; Leonard, WJ
MLA Citation
Puel, A, Ziegler, SF, Buckley, RH, and Leonard, WJ. "Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency." Nat Genet 20.4 (December 1998): 394-397.
PMID
9843216
Source
pubmed
Published In
Nature Genetics
Volume
20
Issue
4
Publish Date
1998
Start Page
394
End Page
397
DOI
10.1038/3877

Unrelated cord blood transplantation for correction of genetic diseases.

Authors
Howrey, RP; Martin, PL; Ciocci, G; Driscoll, TA; Frey, M; Buckley, RH; Hickling, WH; Wiley, J; Provenzale, J; Morse, R; Rubinstein, P; Krivit, W; Kurtzberg, J
MLA Citation
Howrey, RP, Martin, PL, Ciocci, G, Driscoll, TA, Frey, M, Buckley, RH, Hickling, WH, Wiley, J, Provenzale, J, Morse, R, Rubinstein, P, Krivit, W, and Kurtzberg, J. "Unrelated cord blood transplantation for correction of genetic diseases." BLOOD 92.10 (November 15, 1998): 291A-291A.
Source
wos-lite
Published In
Blood
Volume
92
Issue
10
Publish Date
1998
Start Page
291A
End Page
291A

Role of JAK3 in CD40-mediated signaling.

CD40 is a member of the tumor necrosis factor receptor family and plays an important role in B-cell survival, growth, differentiation, and isotype switching. Recently, CD40 has been shown to associate with JAK3, a member of the family of Janus Kinases, which are nonreceptor protein kinases involved in intracellular signaling mediated by cytokines and growth factors. To investigate the role of JAK3 in CD40-mediated signaling, we studied the effect of CD40 stimulation on B-cell proliferation, IgE isotype switching, and upregulation of surface expression of CD23, ICAM-1, CD80, and LT-alpha in JAK3-deficient patients. Our studies show that stimulation of B cells with monoclonal antibody to CD40 in the presence of interleukin-4 (IL-4) or IL-13 resulted in similar responses in JAK3-deficient patients and normal controls. This suggests that JAK3 is not essential for CD40-mediated B-cell proliferation, isotype switching, and upregulation of CD23, ICAM-1, CD80, and LT-alpha surface expression.

Authors
Jabara, HH; Buckley, RH; Roberts, JL; Lefranc, G; Loiselet, J; Khalil, G; Geha, RS
MLA Citation
Jabara, HH, Buckley, RH, Roberts, JL, Lefranc, G, Loiselet, J, Khalil, G, and Geha, RS. "Role of JAK3 in CD40-mediated signaling." Blood 92.7 (October 1, 1998): 2435-2440.
PMID
9746783
Source
pubmed
Published In
Blood
Volume
92
Issue
7
Publish Date
1998
Start Page
2435
End Page
2440

Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9 : 722-728 - Commentary

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9 : 722-728 - Commentary." PEDIATRICS 102.1 (July 1998): 213-215.
PMID
9651432
Source
wos-lite
Published In
Pediatrics
Volume
102
Issue
1
Publish Date
1998
Start Page
213
End Page
215

Hematologic engraftment and reconstitution of immune function post unrelated placental cord blood transplant in an adult with acute lymphocytic leukemia.

Authors
Laughlin, MJ; Rizzieri, DA; Smith, CA; Moore, JO; Lilly, S; McGaughey, D; Martin, P; Carrier, C; Stevens, CE; Rubinstein, P; Buckley, R; Kurtzberg, J
MLA Citation
Laughlin, MJ, Rizzieri, DA, Smith, CA, Moore, JO, Lilly, S, McGaughey, D, Martin, P, Carrier, C, Stevens, CE, Rubinstein, P, Buckley, R, and Kurtzberg, J. "Hematologic engraftment and reconstitution of immune function post unrelated placental cord blood transplant in an adult with acute lymphocytic leukemia." Leuk Res 22.3 (March 1998): 215-219.
PMID
9619913
Source
pubmed
Published In
Leukemia Research
Volume
22
Issue
3
Publish Date
1998
Start Page
215
End Page
219

Complete DiGeorge syndrome: persistence of profound immunodeficiency.

OBJECTIVE: DiGeorge syndrome is characterized by developmental defects of the heart, parathyroid glands, and thymus. The objective of this study was to determine whether T-cell function spontaneously improves in patients with DiGeorge syndrome who have profoundly depressed T-cell proliferative responses to mitogens at presentation, regardless of the T-cell count. STUDY DESIGN: We conducted a retrospective chart review of eight patients with DiGeorge syndrome who had no proliferative responses to mitogens on presentation. RESULTS: Despite lack of responsiveness of the patients' peripheral blood lymphocytes to mitogens, T cells were occasionally detected, and the patients' cells often responded to IL-2 and in mixed lymphocyte reactions. Unresponsiveness to mitogens and clinical immunodeficiency persisted without immune-based therapy. One patient is alive and well after immunoreconstitution from thymic transplantation. The others either died early of complications of their disease such as gastroesophageal reflux with aspiration (2 patients) or infection (2 patients) or died after attempts at immunorestorative therapy with IL-2, thymus transplantation, or bone marrow transplantation (3 patients). CONCLUSION: Eight patients with DiGeorge syndrome who were first seen with no mitogen responsiveness did not improve spontaneously. We recommend HLA-identical bone marrow transplantation or thymic transplantation for these patients as soon as the diagnosis is confirmed.

Authors
Markert, ML; Hummell, DS; Rosenblatt, HM; Schiff, SE; Harville, TO; Williams, LW; Schiff, RI; Buckley, RH
MLA Citation
Markert, ML, Hummell, DS, Rosenblatt, HM, Schiff, SE, Harville, TO, Williams, LW, Schiff, RI, and Buckley, RH. "Complete DiGeorge syndrome: persistence of profound immunodeficiency." J Pediatr 132.1 (January 1998): 15-21.
PMID
9469994
Source
pubmed
Published In
The Journal of Pediatrics
Volume
132
Issue
1
Publish Date
1998
Start Page
15
End Page
21

T cell activation defect presenting with elevated IgE, eczema and severe food allergies

Authors
Daines, MO; Buckley, RH
MLA Citation
Daines, MO, and Buckley, RH. "T cell activation defect presenting with elevated IgE, eczema and severe food allergies." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 101.1 (January 1998): S71-S71.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
101
Issue
1
Publish Date
1998
Start Page
S71
End Page
S71

Influence of host HLA type on mixed leukocyte (ML) responsiveness of haploidentical donor T cells

Authors
Buckley, RH; Carrington, M; Roberts, JL; Riester, D; Ward, FE
MLA Citation
Buckley, RH, Carrington, M, Roberts, JL, Riester, D, and Ward, FE. "Influence of host HLA type on mixed leukocyte (ML) responsiveness of haploidentical donor T cells." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 101.1 (January 1998): S100-S101.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
101
Issue
1
Publish Date
1998
Start Page
S100
End Page
S101

Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online.

The degree of immunodeficiency associated with deficiency of adenosine deaminase (ADA) is variable. Most patients are infants with severe combined immunodeficiency (SCID), but in about 20 percent immune dysfunction becomes manifest later in childhood ("delayed-onset"); several patients with "late" or "adult" onset of immune dysfunction have been diagnosed at 15-39 years. Over 40 ADA gene mutations have thus far been identified. To better define the genotype-phenotype relationship, we report 7 novel ADA mutations, including 5 missense mutations (G74C, V129M, G140E, R149W, Q199P) and two short deletions (462delG, E337del). These were identified among 7 patients (3 with SCID and 4 with delayed-onset). A homozygote for 462delG had SCID, whereas patients homozygous or heterozyous for V129M had delayed-onset. Two other delayed-onset patients, one heterozygous for G74C and the other for Q199P, each had a second allele carrying the previously reported "severe" mutation G216R. These findings are consistent with previous observations suggesting that, in general, SCID occurs when both alleles eliminate ADA function, and a milder phenotype when at least one allele can supply a low level of function.

Authors
Arrendondo-Vega, FX; Santisteban, I; Notarangelo, LD; El Dahr, J; Buckley, R; Roifman, C; Conley, ME; Hershfield, MS
MLA Citation
Arrendondo-Vega, FX, Santisteban, I, Notarangelo, LD, El Dahr, J, Buckley, R, Roifman, C, Conley, ME, and Hershfield, MS. "Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online." Hum Mutat 11.6 (1998): 482-.
PMID
10200056
Source
pubmed
Published In
Human Mutation
Volume
11
Issue
6
Publish Date
1998
Start Page
482
DOI
10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.0.CO;2-E

Role of JAK3 in CD40 mediated signaling

CD40 is a member of the TNF receptor family and plays an important role in B cell survival, growth, differentiation and isotype switching. Recently, CD40 has been shown to associate with JAK3, a member of the Janus Kinase family which are non-receptor protein kinases that are involved in intracellular signaling mediated by cytokines, interferons, and growth factors. To investigate the role of JAK3 in CD40 mediated signalling, we studied the effect of CD40 stimulation of peripheral blood mononuclear cells (PBMC) obtained from JAK3 deficient patients on proliferation, isotype switching, and upregulation of B cell surface expression of CD23 and ICAM-1. Our studies show that stimulation of PBMC with monoclonal antibody to CD40 in the presence of IL-4 or EL-13, resulted in similar profiles in both patients and normal controls in all the above assays. This suggests that JAK3 is not essential for CD40 mediated B cell proliferation, isotype switching, and upregulation of CD23 and ICAM-1 surface expression.

Authors
Jabara, HH; Buckley, RH; Roberts, JL; Lefranc, G; Loiselet, J; Khalil, G; Geha, RS
MLA Citation
Jabara, HH, Buckley, RH, Roberts, JL, Lefranc, G, Loiselet, J, Khalil, G, and Geha, RS. "Role of JAK3 in CD40 mediated signaling." FASEB Journal 12.5 (1998): A923-.
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
12
Issue
5
Publish Date
1998
Start Page
A923

Effect of genetic type of SCID on T, B, and NK cell function following bone marrow stem cell transplantation

The purpose of this study was to evaluate the effect of a mutated microenvironment on the development of T, B and NK cell function in 62 SCIDs following non-ablative T cell-depleted bone marrow stem cell transplantion. 34 SCIDs were γc-deficient, 10 were ADA-deficient, 5 were Jak3-deficient, 11 were autosomal recessive and 2 were of unknown type. Normal T cell function developed(all donor T cells) in all 62 chimeras. However, B cell function remained abnormal in 33, and only 21 had some donor B cells. A majority of the γc-deficient and Jak3-deficient SCIDs had poor B cell function, as demonstrated by failure of isotype-switching following immunization with φX 174, whereas a majority of the ADA-deficient and autosomal recessive SCIDs had good B cell function. Prior to engraftment, a high percentage of B cells in all SCIDs expressed CD1a, CD10, CD5 and CD38; however, γc-deficient and Jak3-deficient B cells had the highest expression of CD1a and the lowest expression of CD38, while B cells from ADA-deficient and autosomal recessive SCIDs had the highest expression of CD38. Post-transplantation, B cell CD1a remained high, CD10 and CD38 declined, and CD5 expression increased. Prior to engraftment, NK cell numbers and function were lowest in γc-deficient and Jak3-deficient SCIDs, whereas they were higher than normal in all other types. Following transplantation, γc- and Jak3-deficients continued to have profoundly low NK numbers and function, while these normalized in all other types. Thus, stem cells that mature in a microenvironment where γc and Jak3 are mutated fail to mature into normal B or NK cells, despite the development of normal T cells and T cell function.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Effect of genetic type of SCID on T, B, and NK cell function following bone marrow stem cell transplantation." FASEB Journal 12.5 (1998): A920-.
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
12
Issue
5
Publish Date
1998
Start Page
A920

Specificity and function of "natural" antibodies in immunodeficient subjects: clues to B cell lineage and development.

The origin of natural antibodies has long been a subject of controversy. Polyreactive natural antibodies recognize multiple ligands and are thought to arise from B1 B cells. Natural antibodies against carbohydrate antigens such as Gal alpha 1-3Gal or against blood groups A and B are thought to be "elicited" by gut bacteria, but their origin is uncertain. To explore the origin of naturally occurring anticarbohydrate antibodies, the specificity and function of the xenoreactive antibodies and isohemagglutinins were investigated in immunodeficient subjects. Subjects with defects in T cell-dependent antibody synthesis had normal levels of xenoreactive natural antibodies, most of which, like xenoreactive antibodies from normal individuals, were specific for Gal alpha 1-3Gal. On the other hand, some subjects with hyper-IgM syndrome who were able to synthesize abundant quantities of xenoreactive antibodies and polyreactive antibodies were devoid of anti-Gal alpha 1-3Gal antibodies. These results suggest that the lineages of B cells giving rise to anti-Gal alpha 1-3Gal antibodies and isohemagglutinins are distinct from B1 B cells or at least exist at a more "advanced" stage of development than those B1 B cells that give rise to polyreactive antibodies. The findings also suggest that B cells which synthesize anti-Gal alpha 1-3Gal antibodies and isohemagglutinins may be distinct from B2 B cells or exist at a more "primitive" stage of development than B2 B cells that synthesize elicited antibodies in normal individuals.

Authors
Parker, W; Yu, PB; Holzknecht, ZE; Lundberg, K; Buckley, RH; Platt, JL
MLA Citation
Parker, W, Yu, PB, Holzknecht, ZE, Lundberg, K, Buckley, RH, and Platt, JL. "Specificity and function of "natural" antibodies in immunodeficient subjects: clues to B cell lineage and development." J Clin Immunol 17.4 (July 1997): 311-321.
PMID
9258770
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
17
Issue
4
Publish Date
1997
Start Page
311
End Page
321

Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is a syndrome of profoundly impaired cellular and humoral immunity. In humans, SCID is most commonly caused by mutations in the X-linked gene IL2RG, which encodes the common gamma chain, gamma c, of the leukocyte receptors for interleukin-2 and multiple other cytokines. To investigate the frequency and variety of IL2RG mutations that cause SCID, we analyzed DNA, RNA, and B-cell lines from a total of 103 unrelated SCID-affected males and their relatives using a combination of molecular and immunologic techniques. Sixty-two different mutations spanning all eight IL2RG exons were found in 87 cases, making possible correlations between mutation type and functional consequences. Although skewed maternal X chromosome inactivation, single-strand conformation polymorphism, mRNA expression, and cell surface staining with anti-gamma c antibodies were all helpful in establishing IL2RG defects as the cause of SCID, only dideoxy fingerprinting and DNA sequence determination each detected 100% of the IL2RG mutations in our series. Abnormal gamma c chains may be expressed in the lymphocytes of as many as two thirds of patients with X-linked SCID. Specific mutation diagnosis thus remains technically challenging, but it is important for genetic counseling and perhaps for helping to select appropriate subjects for retroviral gene therapy trials, This is a US government work. There are no restrictions on its use.

Authors
Puck, JM; Pepper, AE; Henthorn, PS; Candotti, F; Isakov, J; Whitwam, T; Conley, ME; Fischer, RE; Rosenblatt, HM; Small, TN; Buckley, RH
MLA Citation
Puck, JM, Pepper, AE, Henthorn, PS, Candotti, F, Isakov, J, Whitwam, T, Conley, ME, Fischer, RE, Rosenblatt, HM, Small, TN, and Buckley, RH. "Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency." Blood 89.6 (March 15, 1997): 1968-1977.
PMID
9058718
Source
pubmed
Published In
Blood
Volume
89
Issue
6
Publish Date
1997
Start Page
1968
End Page
1977

Gastroesophageal reflux and severe combined immunodeficiency.

BACKGROUND: Gastrointestinal and respiratory symptoms and failure to thrive not associated with infections or medications were noted in patients with severe combined immunodeficiency. OBJECTIVE: The aim of our study was to determine the frequency of gastroesophageal reflux in patients with severe combined immunodeficiency. METHODS: We studied the case histories of 73 pediatric patients who had been treated at Duke University Medical Center for severe combined immunodeficiency between 1982 and 1995. Charts were reviewed for documentation of gastroesophageal reflux on the basis of clinical course and results of barium swallow, esophageal pH probe monitoring, or endoscopy. To compare the incidence of gastroesophageal reflux in patients with severe combined immunodeficiency to known high-risk populations, we additionally tabulated the underlying diagnoses in an age-matched group of patients who underwent Nissen fundoplication from 1990 to 1995. RESULTS: We found clinically significant gastroesophageal reflux in 15 of the 73 patients (20.5%), much higher than has been reported in the normal population (0.1% to 0.3%, p < 0.001). Of patients treated between 1990 and the present, 10 of 36 (27.7%) had significant gastroesophageal reflux compared with five of 37 patients (13.5%) in the previous years. Thus with greater recognition and improved methods for diagnosis, the observed incidence of gastroesophageal reflux has increased greatly. The clinical presentations were not different from those of patients with other well-documented underlying diagnoses. Seven of the 15 patients (46.6%) did not respond to medical treatment with antacids, H2-blockers, and prokinetic agents and underwent surgical treatment. Indications for surgery included persistent esophagitis, vomiting, pneumonia, and growth failure. CONCLUSIONS: The reason for the high incidence of gastroesophageal reflux in patients with severe T-cell disorders remains unclear. Considering the frequency of this association, early recognition and treatment is important to enable adequate nutrition and prevent damage to the esophagus and lungs.

Authors
Boeck, A; Buckley, RH; Schiff, RI
MLA Citation
Boeck, A, Buckley, RH, and Schiff, RI. "Gastroesophageal reflux and severe combined immunodeficiency." J Allergy Clin Immunol 99.3 (March 1997): 420-424.
PMID
9058700
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
99
Issue
3
Publish Date
1997
Start Page
420
End Page
424

Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants.

OBJECTIVE: To determine the relative frequencies of the different genetic forms of severe combined immunodeficiency (SCID) and whether there are distinctive characteristics of the particular genotypes. STUDY DESIGN: The demographic, genetic, and immunologic features of 108 infants with SCID who were treated consecutively at Duke University Medical Center were analyzed. RESULTS: Eighty-nine subjects were boys and 19 were girls; there were 84 white infants, 16 black infants, and 8 Hispanic infants. Forty-nine had X-linked SCID with mutations of common cytokine receptor gamma chain (gamma c), 16 had adenosine deaminase (ADA) deficiency, 8 had Janus kinase 3 (Jak3) deficiency, 21 had unknown autosomal recessive mutations, 1 had reticular dysgenesis, 1 had cartilage hair hypoplasia, and 12 (all boys) had SCID of undetermined type. Deficiency of ADA caused the most profound lymphopenia; gamma c or Jak3 deficiency resulted in the most B cells and fewest natural killer (NK) cells; NK cells and function were highest in autosomal recessive and unknown types of SCID. CONCLUSIONS: Different SCID genotypes are associated with distinctive lymphocyte characteristics. The presence of NK function in ADA-deficient, autosomal recessive, and unknown type SCIDs, and low NK function in a majority of gamma c and Jak3 SCIDs indicates that some molecular lesions affect T, B, and NK cells (gamma c and Jak3), others primarily T cells (ADA deficiency), and others just T and B cells.

Authors
Buckley, RH; Schiff, RI; Schiff, SE; Markert, ML; Williams, LW; Harville, TO; Roberts, JL; Puck, JM
MLA Citation
Buckley, RH, Schiff, RI, Schiff, SE, Markert, ML, Williams, LW, Harville, TO, Roberts, JL, and Puck, JM. "Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants." J Pediatr 130.3 (March 1997): 378-387.
PMID
9063412
Source
pubmed
Published In
The Journal of Pediatrics
Volume
130
Issue
3
Publish Date
1997
Start Page
378
End Page
387

Normalization of the peripheral blood T cell receptor V beta repertoire after cultured postnatal human thymic transplantation in DiGeorge syndrome.

Complete DiGeorge syndrome is an immunodeficiency disease characterized by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transplantation, flow cytometry, T cell receptor V beta sequence analysis, and cell function studies showed the presence of oligoclonal populations of nonfunctional clonally expanded peripheral T cells that were derived from pretransplantation T cells present in the skin. However, at 3 months posttransplantation, a biopsy of the transplanted thymus showed normal intrathymic T cell maturation of host T cells with normal TCR V beta expression on thymocytes. By 9 months postransplantation, peripheral T cell function was restored and the TCR V beta repertoire became polyclonal, coincident with the appearance of normal T cell function. These data suggest that the transplanted thymus was responsible for the establishment of a new T cell repertoire via thymopoiesis in the chimeric thymic graft.

Authors
Davis, CM; McLaughlin, TM; Watson, TJ; Buckley, RH; Schiff, SE; Hale, LP; Haynes, BF; Markert, ML
MLA Citation
Davis, CM, McLaughlin, TM, Watson, TJ, Buckley, RH, Schiff, SE, Hale, LP, Haynes, BF, and Markert, ML. "Normalization of the peripheral blood T cell receptor V beta repertoire after cultured postnatal human thymic transplantation in DiGeorge syndrome." J Clin Immunol 17.2 (March 1997): 167-175.
PMID
9083893
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
17
Issue
2
Publish Date
1997
Start Page
167
End Page
175

Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus.

Transplantation of cultured postnatal human thymus was performed in a patient with complete DiGeorge syndrome. Biopsy of the graft 3 mo after implantation revealed normal CD1+ thymocytes in thymic cortical epithelial regions and CD1- thymocytes in thymic medullary epithelial regions, respectively. HLA analysis of graft thymocyte and thymic microenvironment components demonstrated that developing thymocytes and thymic macrophages were recipient derived, while thymic epithelial components were of donor origin. The patient, who initially had no T cells and had profoundly defective T cell function, developed normal T cell responses to mitogens and Ags, tolerance to donor in a mixed lymphocyte reaction, and normal Ab titers after tetanus toxoid and pneumovax immunization. Thus, transplantation of cultured postnatal human thymic tissue in humans can form functional chimeric thymic tissue, and may provide a strategy to reconstitute the peripheral T cell pool in select congenital and acquired immune deficiency syndromes.

Authors
Markert, ML; Kostyu, DD; Ward, FE; McLaughlin, TM; Watson, TJ; Buckley, RH; Schiff, SE; Ungerleider, RM; Gaynor, JW; Oldham, KT; Mahaffey, SM; Ballow, M; Driscoll, DA; Hale, LP; Haynes, BF
MLA Citation
Markert, ML, Kostyu, DD, Ward, FE, McLaughlin, TM, Watson, TJ, Buckley, RH, Schiff, SE, Ungerleider, RM, Gaynor, JW, Oldham, KT, Mahaffey, SM, Ballow, M, Driscoll, DA, Hale, LP, and Haynes, BF. "Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus." J Immunol 158.2 (January 15, 1997): 998-1005.
PMID
8993022
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
158
Issue
2
Publish Date
1997
Start Page
998
End Page
1005

Multicenter crossover comparison of the safety and efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in patients with primary immunodeficiency diseases.

The safety and clinical efficacy of a liquid, beta-propiolactone-stabilized intravenous gamma-globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. beta-Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous gamma-globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.

Authors
Schiff, RI; Williams, LW; Nelson, RP; Buckley, RH; Burks, W; Good, RA
MLA Citation
Schiff, RI, Williams, LW, Nelson, RP, Buckley, RH, Burks, W, and Good, RA. "Multicenter crossover comparison of the safety and efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in patients with primary immunodeficiency diseases." J Clin Immunol 17.1 (January 1997): 21-28.
PMID
9049782
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
17
Issue
1
Publish Date
1997
Start Page
21
End Page
28

Responsiveness of SCID lymphocytes to anti-CD3, PMA and Ionomycin before and after bone marrow transplantation.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Responsiveness of SCID lymphocytes to anti-CD3, PMA and Ionomycin before and after bone marrow transplantation." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 99.1 (January 1997): 412-412.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
99
Issue
1
Publish Date
1997
Start Page
412
End Page
412

Complete DiGeorge syndrome: Persistence of profound immunodeficiency.

Authors
Markert, ML; Watson, TJ; McLaughlin, TM; Hummel, DS; Rosenblatt, HM; Schiff, SE; Harville, TO; Williams, L; Schiff, RI; Buckley, RH
MLA Citation
Markert, ML, Watson, TJ, McLaughlin, TM, Hummel, DS, Rosenblatt, HM, Schiff, SE, Harville, TO, Williams, L, Schiff, RI, and Buckley, RH. "Complete DiGeorge syndrome: Persistence of profound immunodeficiency." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 99.1 (January 1997): 1599-1599.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
99
Issue
1
Publish Date
1997
Start Page
1599
End Page
1599

Clinical features in patients with mutations in the immunoglobulin mu heavy chain gene.

Authors
Yel, L; Trubel, H; Buckley, RH; Pachman, LM; Conley, ME
MLA Citation
Yel, L, Trubel, H, Buckley, RH, Pachman, LM, and Conley, ME. "Clinical features in patients with mutations in the immunoglobulin mu heavy chain gene." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 99.1 (January 1997): 1927-1927.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
99
Issue
1
Publish Date
1997
Start Page
1927
End Page
1927

Bone marrow transplantation for SCID in the neonatal period.

Authors
Myers, LA; Riester, DE; Schiff, RI; Schiff, SE; Williams, LW; Roberts, JL; Puck, JM; Buckley, RH
MLA Citation
Myers, LA, Riester, DE, Schiff, RI, Schiff, SE, Williams, LW, Roberts, JL, Puck, JM, and Buckley, RH. "Bone marrow transplantation for SCID in the neonatal period." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 99.1 (January 1997): 411-411.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
99
Issue
1
Publish Date
1997
Start Page
411
End Page
411

Mutations in the mu heavy-chain gene in patients with agammaglobulinemia.

BACKGROUND: Most patients with congenital hypogammaglobulinemia and absent B cells are males with X-linked agammaglobulinemia, which is caused by mutations in the gene for Bruton's tyrosine kinase (Btk); however, there are females with a similar disorder who do not have mutations in this gene. We studied two families with autosomal recessive defects in B-cell development and patients with presumed X-linked agammaglobulinemia who did not have mutations in Btk. METHODS: A series of candidate genes that encode proteins involved in B-cell signal-transduction pathways were analyzed by linkage studies and mutation screening. RESULTS: Four different mutations were identified in the mu heavy-chain gene on chromosome 14. In one family, there was a homozygous 75-to-100-kb deletion that included D-region genes, J-region genes, and the mu constant-region gene. In a second family, there was a homozygous base-pair substitution in the alternative splice site of the mu heavy-chain gene. This mutation would inhibit production of the membrane form of the mu chain and produce an amino acid substitution in the secreted form. In addition, a patient previously thought to have X-linked agammaglobulinemia was found to have an amino acid substitution on one chromosome at an invariant cysteine that is required for the intrachain disulfide bond and, on the other chromosome, a large deletion that included the immunoglobulin locus. CONCLUSIONS: Defects in the mu heavy-chain gene are a cause of agammaglobulinemia in humans. This implies that an intact membrane-bound mu chain is essential for B-cell development.

Authors
Yel, L; Minegishi, Y; Coustan-Smith, E; Buckley, RH; Trübel, H; Pachman, LM; Kitchingman, GR; Campana, D; Rohrer, J; Conley, ME
MLA Citation
Yel, L, Minegishi, Y, Coustan-Smith, E, Buckley, RH, Trübel, H, Pachman, LM, Kitchingman, GR, Campana, D, Rohrer, J, and Conley, ME. "Mutations in the mu heavy-chain gene in patients with agammaglobulinemia." N Engl J Med 335.20 (November 14, 1996): 1486-1493.
PMID
8890099
Source
pubmed
Published In
The New England journal of medicine
Volume
335
Issue
20
Publish Date
1996
Start Page
1486
End Page
1493
DOI
10.1056/NEJM199611143352003

Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia.

Review of the medical records of 43 patients with common variable immunodeficiency (CVID) and 23 patients with X-linked agammaglobulinemia (XLAG) revealed a high incidence of chronic gastrointestinal complaints, most commonly diarrhea. Thirty-eight biopsies, four small-bowel resection specimens, and one autopsy from 10 patients with CVID and one patient with XLAG showed a wide range of abnormalities. A pattern resembling acute graft-versus-host disease, with apoptotic bodies and lymphocytes in crypts, was seen in the stomach (four patients), small bowel (three patients), and colon (three patients). Small-bowel specimens from three CVID patients with malabsorption showed mild to severe villous atrophy. Three CVID patients had Giardia in biopsies. Two cases of small bowel lymphoma associated with nodular lymphoid hyperplasia were identified in CVID patients. One patient's small bowel contained foamy histiocytes in the lamina propria, resembling Whipple's disease or chronic granulomatous disease, with numerous apoptotic bodies in crypts. Ultrastructurally, the histiocytes contained cellular debris. The patient with XLAG had recurrent fissuring necrosis of small bowel resembling Crohn's disease; a patient with CVID had colitis with features similar to ulcerative colitis. Poorly formed granulomas were seen in the stomach (one CVID patient) and the colon (two CVID patients). Lymphocyte populations were dominated by T cells; B cells were scarce except in lymphoid follicles in CVID patients with nodular lymphoid hyperplasia. Patients with CVID and XLAG manifest a spectrum of abnormalities in the gastrointestinal tract, with patterns superficially resembling graft-versus-host disease, inflammatory bowel disease, and Whipple's disease, but often lacking some of the diagnostic features of the diseases. Many of the CVID patients with chronic gastrointestinal complaints (62%) also had evidence of autoimmune phenomena, suggesting that in some patients the inflammatory process in the gastrointestinal tract has an autoimmune component.

Authors
Washington, K; Stenzel, TT; Buckley, RH; Gottfried, MR
MLA Citation
Washington, K, Stenzel, TT, Buckley, RH, and Gottfried, MR. "Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia." Am J Surg Pathol 20.10 (October 1996): 1240-1252.
PMID
8827031
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
20
Issue
10
Publish Date
1996
Start Page
1240
End Page
1252

Thymic transplantation for digeorge syndrome.

Authors
Markert, ML; Davis, CM; Ward, FE; Kostyu, DD; Buckley, RH; Schiff, SE; Watson, TJ; McLaughlin, TM; Hale, LP; Ballow, M; Haynes, BF
MLA Citation
Markert, ML, Davis, CM, Ward, FE, Kostyu, DD, Buckley, RH, Schiff, SE, Watson, TJ, McLaughlin, TM, Hale, LP, Ballow, M, and Haynes, BF. "Thymic transplantation for digeorge syndrome." FASEB JOURNAL 10.6 (April 30, 1996): 373-373.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
10
Issue
6
Publish Date
1996
Start Page
373
End Page
373

Human autosomal recessive SCID due to Jak3 deficiency.

Authors
Roberts, JL; OShea, II; Puck, JM; Buckley, RH
MLA Citation
Roberts, JL, OShea, II, Puck, JM, and Buckley, RH. "Human autosomal recessive SCID due to Jak3 deficiency." FASEB JOURNAL 10.6 (April 30, 1996): 370-370.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
10
Issue
6
Publish Date
1996
Start Page
370
End Page
370

Human severe combined immunodeficiency (SCID): Genetic, phenotypic and functional diversity in 95 infants.

Authors
Buckley, RH; Schiff, RE; Schiff, SE; Markert, ML; Williams, LW; Harville, TO; Roberts, JL; Puck, J
MLA Citation
Buckley, RH, Schiff, RE, Schiff, SE, Markert, ML, Williams, LW, Harville, TO, Roberts, JL, and Puck, J. "Human severe combined immunodeficiency (SCID): Genetic, phenotypic and functional diversity in 95 infants." PEDIATRIC RESEARCH 39.4 (April 1996): 41-41.
Source
wos-lite
Published In
Pediatric Research
Volume
39
Issue
4
Publish Date
1996
Start Page
41
End Page
41

Practice parameters for the diagnosis and management of immunodeficiency. The Clinical and Laboratory Immunology Committee of the American Academy of Allergy, Asthma, and Immunology (CLIC-AAAAI)

In this brief review, only the most useful immunologic tests available for defining host defects that lead to susceptibility to infection have been emphasized. It should be pointed out that those evaluations and tests ordered by the physician will rule out the vast majority of the currently recognized defects. Finally, it is important that any patients identified as abnormal by these screening tests be characterized as fully as possible in centers specializing in these diseases before therapy is initiated, since what may appear to be a simple diagnosis on the surface may be an indicator of more complex underlying problems.

Authors
Shearer, WT; Buckley, RH; Engler, RJ; Finn, AF; Fleisher, TA; Freeman, TM; Herrod, HG; Levinson, AI; Lopez, M; Rich, RR; Rosenfeld, SI; Rosenwasser, LJ
MLA Citation
Shearer, WT, Buckley, RH, Engler, RJ, Finn, AF, Fleisher, TA, Freeman, TM, Herrod, HG, Levinson, AI, Lopez, M, Rich, RR, Rosenfeld, SI, and Rosenwasser, LJ. "Practice parameters for the diagnosis and management of immunodeficiency. The Clinical and Laboratory Immunology Committee of the American Academy of Allergy, Asthma, and Immunology (CLIC-AAAAI)." Ann Allergy Asthma Immunol 76.3 (March 1996): 282-294.
PMID
8634885
Source
pubmed
Published In
Annals of Allergy, Asthma & Immunology
Volume
76
Issue
3
Publish Date
1996
Start Page
282
End Page
294

Correction of purine nucleoside phosphorylase deficiency by transplantation of allogeneic bone marrow from a sibling.

Deficiency of the purine salvage pathway enzyme purine nucleoside phosphorylase causes a combined immunodeficiency and neurologic abnormalities and is usually fatal in childhood. We report the first successful transplantation of bone marrow from a sibling with identical class II human leukocyte antigens in this condition, demonstrating correction of both lymphocyte metabolic and functional abnormalities.

Authors
Broome, CB; Graham, ML; Saulsbury, FT; Hershfield, MS; Buckley, RH
MLA Citation
Broome, CB, Graham, ML, Saulsbury, FT, Hershfield, MS, and Buckley, RH. "Correction of purine nucleoside phosphorylase deficiency by transplantation of allogeneic bone marrow from a sibling." J Pediatr 128.3 (March 1996): 373-376.
PMID
8774508
Source
pubmed
Published In
The Journal of Pediatrics
Volume
128
Issue
3
Publish Date
1996
Start Page
373
End Page
376

Practice parameters for the diagnosis and management of immunodeficiency

Authors
Shearer, WT; Buckley, RH; Engler, RJM; Jr, AFF; Fleisher, TA; Freeman, TM; III, HGH; Levinson, AI; Lopez, M; Rich, RR; Rosenfeld, SI; Rosenwasser, LJ
MLA Citation
Shearer, WT, Buckley, RH, Engler, RJM, Jr, AFF, Fleisher, TA, Freeman, TM, III, HGH, Levinson, AI, Lopez, M, Rich, RR, Rosenfeld, SI, and Rosenwasser, LJ. "Practice parameters for the diagnosis and management of immunodeficiency." Annals of Allergy, Asthma and Immunology 76.3 (1996): 282-294.
Source
scival
Published In
Annals of Allergy, Asthma & Immunology
Volume
76
Issue
3
Publish Date
1996
Start Page
282
End Page
294

Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.

Males with X-linked severe combined immunodeficiency (XSCID) have defects in the common cytokine receptor gamma chain (gamma c) gene that encodes a shared, essential component of the receptors of interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15. The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c, so it was hypothesized that defects in Jak3 might cause an XSCID-like phenotype. A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis. An Epstein-Barr virus (EBV)-transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA. Sequencing revealed a different mutation on each allele: a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain. The lack of Jak3 expression correlated with impaired B cell signaling, as demonstrated by the inability of IL-4 to activate Stat6 in the EBV-transformed cell line from the patient. These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.

Authors
Russell, SM; Tayebi, N; Nakajima, H; Riedy, MC; Roberts, JL; Aman, MJ; Migone, TS; Noguchi, M; Markert, ML; Buckley, RH; O'Shea, JJ; Leonard, WJ
MLA Citation
Russell, SM, Tayebi, N, Nakajima, H, Riedy, MC, Roberts, JL, Aman, MJ, Migone, TS, Noguchi, M, Markert, ML, Buckley, RH, O'Shea, JJ, and Leonard, WJ. "Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development." Science 270.5237 (November 3, 1995): 797-800.
PMID
7481768
Source
pubmed
Published In
Science
Volume
270
Issue
5237
Publish Date
1995
Start Page
797
End Page
800

DEVELOPMENT OF T-CELL FUNCTION AFTER POSTNATAL THYMIC TRANSPLANTATION FOR DIGEORGE-SYNDROME

Authors
MARKERT, ML; WATSON, TJ; MCLAUGHLIN, TM; MCGUIRE, CA; WARD, FE; KOSTYU, D; HALE, LP; BUCKLEY, RH; SCHIFF, SE; BLEESING, JJH; BROOME, CB; UNGERLEIDER, RM; MAHAFFEY, SM; OLDHAM, KT; HAYNES, BF
MLA Citation
MARKERT, ML, WATSON, TJ, MCLAUGHLIN, TM, MCGUIRE, CA, WARD, FE, KOSTYU, D, HALE, LP, BUCKLEY, RH, SCHIFF, SE, BLEESING, JJH, BROOME, CB, UNGERLEIDER, RM, MAHAFFEY, SM, OLDHAM, KT, and HAYNES, BF. "DEVELOPMENT OF T-CELL FUNCTION AFTER POSTNATAL THYMIC TRANSPLANTATION FOR DIGEORGE-SYNDROME." AMERICAN JOURNAL OF HUMAN GENETICS 57.4 (October 1995): 64-64.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
57
Issue
4
Publish Date
1995
Start Page
64
End Page
64

Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.

Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor gamma chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute > 20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations.

Authors
Pepper, AE; Buckley, RH; Small, TN; Puck, JM
MLA Citation
Pepper, AE, Buckley, RH, Small, TN, and Puck, JM. "Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency." Am J Hum Genet 57.3 (September 1995): 564-571.
PMID
7668284
Source
pubmed
Published In
The American Journal of Human Genetics
Volume
57
Issue
3
Publish Date
1995
Start Page
564
End Page
571

2 MUTATIONAL HOTSPOTS IN THE INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN GENE CAUSING HUMAN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY

Authors
PEPPER, AE; BUCKLEY, RH; SMALL, TN; PUCK, JM
MLA Citation
PEPPER, AE, BUCKLEY, RH, SMALL, TN, and PUCK, JM. "2 MUTATIONAL HOTSPOTS IN THE INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN GENE CAUSING HUMAN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY." AMERICAN JOURNAL OF HUMAN GENETICS 57.3 (September 1995): 564-571.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
57
Issue
3
Publish Date
1995
Start Page
564
End Page
571

DEVELOPMENT OF T-CELL FUNCTION AFTER POSTNATAL THYMIC TRANSPLANTATION FOR DIGEORGE-SYNDROME

Authors
MARKERT, ML; WARD, FE; KOSTYU, D; BUCKLEY, RH; SCHIFF, SE; BLEESING, JJH; BROOME, CB; UNGERLEIDER, RM; GAYNOR, JW; MAHAFFEY, SM; OLDHAM, KT; WATSON, TJ; MCLAUGHLIN, TM; HAYNES, BF
MLA Citation
MARKERT, ML, WARD, FE, KOSTYU, D, BUCKLEY, RH, SCHIFF, SE, BLEESING, JJH, BROOME, CB, UNGERLEIDER, RM, GAYNOR, JW, MAHAFFEY, SM, OLDHAM, KT, WATSON, TJ, MCLAUGHLIN, TM, and HAYNES, BF. "DEVELOPMENT OF T-CELL FUNCTION AFTER POSTNATAL THYMIC TRANSPLANTATION FOR DIGEORGE-SYNDROME." FASEB JOURNAL 9.4 (March 10, 1995): A780-A780.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
9
Issue
4
Publish Date
1995
Start Page
A780
End Page
A780

IMMUNOBIOLOGY OF HUMAN SEVERE COMBINED IMMUNODEFICIENCY

Authors
BUCKLEY, RH; SCHIFF, RI; MARKERT, ML; WILLIAMS, LW; HARVILLE, TO; SCHIFF, SE
MLA Citation
BUCKLEY, RH, SCHIFF, RI, MARKERT, ML, WILLIAMS, LW, HARVILLE, TO, and SCHIFF, SE. "IMMUNOBIOLOGY OF HUMAN SEVERE COMBINED IMMUNODEFICIENCY." FASEB JOURNAL 9.4 (March 10, 1995): A780-A780.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
9
Issue
4
Publish Date
1995
Start Page
A780
End Page
A780

SUCCESSFUL BONE-MARROW TRANSPLANTATION (BMT) FOR PURINE NUCLEOSIDE PHOSPHORYLASE (PNP) DEFICIENCY

Authors
BROOME, CB; GRAHAM, ML; SAULSBURY, FT; HERSHFIELD, MS; BUCKLEY, RH
MLA Citation
BROOME, CB, GRAHAM, ML, SAULSBURY, FT, HERSHFIELD, MS, and BUCKLEY, RH. "SUCCESSFUL BONE-MARROW TRANSPLANTATION (BMT) FOR PURINE NUCLEOSIDE PHOSPHORYLASE (PNP) DEFICIENCY." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 95.1 (January 1995): 142-142.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
95
Issue
1
Publish Date
1995
Start Page
142
End Page
142

The hyper-IgE syndrome

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The hyper-IgE syndrome." 1995.
Source
wos-lite
Published In
International Congress Series
Volume
1073
Publish Date
1995
Start Page
21
End Page
26

Breakthroughs in the understanding and therapy of primary immunodeficiency

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Breakthroughs in the understanding and therapy of primary immunodeficiency." 1995.
Source
wos-lite
Published In
International Congress Series
Volume
1073
Publish Date
1995
Start Page
293
End Page
299

ATYPICAL X-LINKED AGAMMAGLOBULINEMIA - REPLY

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "ATYPICAL X-LINKED AGAMMAGLOBULINEMIA - REPLY." NEW ENGLAND JOURNAL OF MEDICINE 331.14 (October 6, 1994): 950-951.
Source
wos-lite
Published In
The New England journal of medicine
Volume
331
Issue
14
Publish Date
1994
Start Page
950
End Page
951

Hyper IgM syndrome associated with defective CD40-mediated B cell activation.

Recent studies show that most patients with X-linked hyper IgM syndrome have defects in the gene for CD40 ligand. We evaluated 17 unrelated males suspected of having X-linked hyper IgM syndrome. Activated T cells from 13 of the 17 patients failed to bind a soluble CD40 construct. In these patients, the sequence of CD40 ligand demonstrated mutations. By contrast, T cells from the remaining four patients exhibited normal binding to the CD40 construct. Sequencing of the cDNA for CD40 ligand from these patients did not show mutations. The possibility that hyper IgM syndrome in these four patients was due to abnormalities in the B cell response to CD40-mediated signals was examined. Peripheral blood lymphocytes were stimulated with anti-CD40 alone, IL4 alone or anti-CD40 plus IL4. In comparison with B cells from controls or patients with hyper IgM syndrome and mutant CD40 ligand, B cells from the patients with hyper IgM syndrome and normal CD40 ligand were defective in their ability to secrete IgE (P < 0.02) or express activation markers, CD25 and CD23 (P < 0.02) in response to stimulation with anti-CD40. The failure of these B cells to respond to CD40-mediated activation could not be attributed to a generalized deficiency in B cell activation because IL4 induced normal up-regulation of CD23 and CD25 expression. These findings indicate that hyper IgM syndrome may result from defects in expression of CD40 ligand by activated T cells or defects in CD40-mediated signal transduction in B cells.

Authors
Conley, ME; Larché, M; Bonagura, VR; Lawton, AR; Buckley, RH; Fu, SM; Coustan-Smith, E; Herrod, HG; Campana, D
MLA Citation
Conley, ME, Larché, M, Bonagura, VR, Lawton, AR, Buckley, RH, Fu, SM, Coustan-Smith, E, Herrod, HG, and Campana, D. "Hyper IgM syndrome associated with defective CD40-mediated B cell activation." J Clin Invest 94.4 (October 1994): 1404-1409.
PMID
7523449
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
94
Issue
4
Publish Date
1994
Start Page
1404
End Page
1409
DOI
10.1172/JCI117476

Breakthroughs in the understanding and therapy of primary immunodeficiency.

In the 40 years since Ogden Bruton discovered agammaglobulinemia, more than 50 additional immunodeficiency syndromes have been described. Until recently, there was little insight into the fundamental problems underlying a majority of these conditions. Recently, however, the molecular bases of three X-linked immunodeficiency disorders have been reported. These include X-linked immunodeficiency with hyper IgM, X-linked agammaglobulinemia, and X-linked severe combined immunodeficiency. These remarkable accomplishments have been made possible through a combination of new knowledge of molecular signaling mechanisms between and within cells of the immune system and greatly improved approaches to disease loci mapping within the human genome. Improvements in the therapy of immunodeficiency diseases have been impressive, and the development of generally safe and effective intravenous immunoglobulin preparations and T cell depletion techniques that permit the use of non-HLA-identical bone marrow donors have been the most important advances over the past 14 years. The identification and cloning of the genes for several of the primary immunodeficiency diseases have obvious implications for potential future somatic cell gene therapy for these patients. The rapidity of these advances suggests that soon there will be many more to come.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Breakthroughs in the understanding and therapy of primary immunodeficiency." Pediatr Clin North Am 41.4 (August 1994): 665-690. (Review)
PMID
8047366
Source
pubmed
Published In
Pediatric Clinics of North America
Volume
41
Issue
4
Publish Date
1994
Start Page
665
End Page
690

Growth-dependent regulation of cellular ceramides in human T-cells.

The role of ceramide, a putative lipid second messenger in the regulation of cell growth, was investigated in T-lymphocytes. An inverse relationship between the cellular concentrations of ceramide and the proliferative capacity of human T-lymphocytes was observed for cells treated with either interleukin-2 or phorbol ester plus ionomycin. The same relationship between cellular ceramide concentrations and DNA synthesis also was observed for cells derived from a cultured T-cell line, the Jurkat T-cells. Alternative approaches for modulating the cellular ceramide concentrations were employed to determine the relationship between sphingolipids and cell growth. Treatment of normal T-lymphocyte cultures with exogenous cell-permeable ceramide analogues or sphingosine stereoisomers decreased DNA synthesis. A similar effect was seen with stearylamine. Cells treated with D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of UDP-glucosyl:ceramide transferase, accumulated cellular ceramide concentrations and had decreased DNA synthesis. These results define a correlation between the concentration of cellular ceramides and the capacity of T-lymphocytes to proliferate. However, the addition of bacterial sphingomyelinase to the T-cell medium caused an increase in ceramide concentrations (presumably at the plasma membrane), which did not affect cell growth. These results support the hypothesis that functionally distinct pools of ceramide may reside within the T-cell.

Authors
Borchardt, RA; Lee, WT; Kalen, A; Buckley, RH; Peters, C; Schiff, S; Bell, RM
MLA Citation
Borchardt, RA, Lee, WT, Kalen, A, Buckley, RH, Peters, C, Schiff, S, and Bell, RM. "Growth-dependent regulation of cellular ceramides in human T-cells." Biochim Biophys Acta 1212.3 (June 2, 1994): 327-336.
PMID
8199203
Source
pubmed
Published In
Biochimica et Biophysica Acta: international journal of biochemistry and biophysics
Volume
1212
Issue
3
Publish Date
1994
Start Page
327
End Page
336

Assessing inheritance of agammaglobulinemia.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Assessing inheritance of agammaglobulinemia." N Engl J Med 330.21 (May 26, 1994): 1526-1528.
PMID
8164707
Source
pubmed
Published In
The New England journal of medicine
Volume
330
Issue
21
Publish Date
1994
Start Page
1526
End Page
1528
DOI
10.1056/NEJM199405263302111

POLYCLONAL MATERNAL T-LYMPHOCYTES ARE PRESENT IN INFANTS WITH SEVERE COMBINED IMMUNODEFICIENCY (SCID) PRIOR TO BONE-MARROW TRANSPLANTATION (BMT)

Authors
HARVILLE, TO; NORVELL, KE; BUCKLEY, RH
MLA Citation
HARVILLE, TO, NORVELL, KE, and BUCKLEY, RH. "POLYCLONAL MATERNAL T-LYMPHOCYTES ARE PRESENT IN INFANTS WITH SEVERE COMBINED IMMUNODEFICIENCY (SCID) PRIOR TO BONE-MARROW TRANSPLANTATION (BMT)." PEDIATRIC RESEARCH 35.4 (April 1994): A11-A11.
Source
wos-lite
Published In
Pediatric Research
Volume
35
Issue
4
Publish Date
1994
Start Page
A11
End Page
A11

IGE SYNTHESIS BY B-CELLS FROM IMMUNODEFICIENCY PATIENTS

Authors
BUCKLEY, RH; KLUGE, J; LEVINE, A
MLA Citation
BUCKLEY, RH, KLUGE, J, and LEVINE, A. "IGE SYNTHESIS BY B-CELLS FROM IMMUNODEFICIENCY PATIENTS." FASEB JOURNAL 8.5 (March 18, 1994): A752-A752.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
8
Issue
5
Publish Date
1994
Start Page
A752
End Page
A752

Atypical X-linked agammaglobulinemia [3]

Authors
Kornfeld, SJ; Good, RA; Litman, GW; Parolini, O; Rohrer, J; Conley, ME; Buckley, RH
MLA Citation
Kornfeld, SJ, Good, RA, Litman, GW, Parolini, O, Rohrer, J, Conley, ME, and Buckley, RH. "Atypical X-linked agammaglobulinemia [3]." New England Journal of Medicine 331.14 (1994): 949-951.
PMID
8078565
Source
scival
Published In
New England Journal of Medicine
Volume
331
Issue
14
Publish Date
1994
Start Page
949
End Page
951
DOI
10.1056/NEJM199410063311416

Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency.

From May 1992 to March 1993, 50 infants with severe combined immunodeficiency (SCID) were given bone marrow transplants at Duke University Medical Center. None received chemotherapy for conditioning or for graft-versus-host disease (GVHD) prophylaxis. Forty-one received haploidentical parental marrow depleted of T cells by soybean lectin and sheep red blood cell resetting, and nine received HLA-identical marrow. Forty (80%) survived from 1 week to almost 11 years posttransplantation, including nine of nine (100%) HLA-identical marrow recipients and 31 of 41 haploidentical recipients. T-cell function was present within 2 weeks after transplantation of unfractionated HLA-identical marrow, but not until 3 to 4 months after T-cell-depleted haploidentical marrow stem cells. All 37 patients who are more than 4 months posttransplantation have good T-cell function, and all but one have 100% donor T cells. B-cell function developed slowly or not at all in some recipients of haploidentical marrow. Fourteen (four HLA-identical and 10 haploidentical recipients) have some donor B cells; 19 patients are receiving intravenous immune globulin (IVIG) therapy.

Authors
Buckley, RH; Schiff, SE; Schiff, RI; Roberts, JL; Markert, ML; Peters, W; Williams, LW; Ward, FE
MLA Citation
Buckley, RH, Schiff, SE, Schiff, RI, Roberts, JL, Markert, ML, Peters, W, Williams, LW, and Ward, FE. "Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency." Semin Hematol 30.4 Suppl 4 (October 1993): 92-101. (Review)
PMID
7905667
Source
pubmed
Published In
Seminars in Hematology
Volume
30
Issue
4 Suppl 4
Publish Date
1993
Start Page
92
End Page
101

HAPLOIDENTICAL BONE-MARROW STEM-CELL TRANSPLANTATION IN HUMAN SEVERE COMBINED IMMUNODEFICIENCY

Authors
BUCKLEY, RH; SCHIFF, SE; SCHIFF, RI; ROBERTS, JL; MARKERT, ML; PETERS, W; WILLIAMS, LW; WARD, FE
MLA Citation
BUCKLEY, RH, SCHIFF, SE, SCHIFF, RI, ROBERTS, JL, MARKERT, ML, PETERS, W, WILLIAMS, LW, and WARD, FE. "HAPLOIDENTICAL BONE-MARROW STEM-CELL TRANSPLANTATION IN HUMAN SEVERE COMBINED IMMUNODEFICIENCY." October 1993.
Source
wos-lite
Published In
Seminars in Hematology
Volume
30
Issue
4
Publish Date
1993
Start Page
92
End Page
104

HAPLOIDENTICAL STEM-CELL THERAPY FOR HUMAN SEVERE COMBINED IMMUNODEFICIENCY (SCID) - ANALYSIS AT 10 YEARS

Authors
BUCKLEY, RH; SCHIFF, SE; SCHIFF, RI; MARKERT, ML; WILLIAMS, LW; WARD, FE
MLA Citation
BUCKLEY, RH, SCHIFF, SE, SCHIFF, RI, MARKERT, ML, WILLIAMS, LW, and WARD, FE. "HAPLOIDENTICAL STEM-CELL THERAPY FOR HUMAN SEVERE COMBINED IMMUNODEFICIENCY (SCID) - ANALYSIS AT 10 YEARS." CLINICAL RESEARCH 41.2 (April 1993): A278-A278.
Source
wos-lite
Published In
Clinical Research
Volume
41
Issue
2
Publish Date
1993
Start Page
A278
End Page
A278

Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency

From May 1992 to March 1993, 50 infants with severe combined immunodeficiency (SCID) were given bone marrow transplants at Duke University Medical Center. None received chemotherapy for conditioning or for graft- versus-host disease (GVHD) prophylaxis. Forty-one received haploidentical parental marrow depleted of T cells by soybean lectin and sheep red blood cell resetting, and nine received HLA-identical marrow. Forty (80%) survived from 1 week to almost 11 years postransplantation, including nine of nine (100%) HLA-identical marrow recipients and 31 of 41 haploidentical recipients. T-cell function was present within 2 weeks after transplantation of unfractionated HLA-identical marrow, but not until 3 to 4 months after T- cell-depleted haploidentical marrow stem cells. All 37 patients who are more than 4 months posttransplantation have good T-cell function, and all but one have 100% donor T cells. B-cell function developed slowly or not at all in some recipients of haploidentical marrow. Fourteen (four HLA-identical and 10 haploidentical recipients) have some donor B cells; 19 patients are receiving intravenous immune globulin (IVIG) therapy.

Authors
Buckley, RH; Schiff, SE; Schiff, RI; Roberts, JL; Markert, ML; Peters, W; Williams, LW; Ward, FE; Ballow, ; Boxer, ; Strober, ; McGhee, ; Schwartz, ; Nelson, ; Puck, ; Ochs, ; Parkman, ; Deeg,
MLA Citation
Buckley, RH, Schiff, SE, Schiff, RI, Roberts, JL, Markert, ML, Peters, W, Williams, LW, Ward, FE, Ballow, , Boxer, , Strober, , McGhee, , Schwartz, , Nelson, , Puck, , Ochs, , Parkman, , and Deeg, . "Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency." Seminars in Hematology 30.4 SUPPL. 4 (1993): 92-104.
Source
scival
Published In
Seminars in Hematology
Volume
30
Issue
4 SUPPL. 4
Publish Date
1993
Start Page
92
End Page
104

Immunodeficiency diseases.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Immunodeficiency diseases." JAMA 268.20 (November 25, 1992): 2797-2806. (Review)
PMID
1433695
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
268
Issue
20
Publish Date
1992
Start Page
2797
End Page
2806

Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency and its biochemical consequences cause severe combined immunodeficiency (SCID). Treatment strategies, designed to correct the biochemical abnormalities, include transplantation of matched bone marrow or haploidentical bone marrow stem cells, repeated partial exchange transfusions with frozen irradiated human red blood cells (RBC), or weekly injection of polyethylene glycol-modified bovine ADA (PEG-ADA). To evaluate the effect of these therapeutic options, we studied in vitro T-cell function and in vivo antibody responses to the T-cell-dependent neoantigen, bacteriophage phi X174, in 10 children with ADA-deficient SCID. In untreated patients, T-cell function was severely depressed, and only minute amounts of antibacteriophage antibody were produced. Transplantation of bone marrow from a matched sibling (one patient) or a phenotypically matched parent (one patient) resulted in a stable graft, normal T-cell function, and substantial but subnormal antibody titers to bacteriophage, with reduced memory and impaired switch from IgM to IgG. Patients receiving T-cell-depleted haploidentical bone marrow stem cells had markedly depressed antibody responses for as long as 3 years posttransplantation, despite rapidly improving T-cell function that became normal in two of four patients. Two methods of enzyme replacement were explored. During treatment with human RBC transfusions, antibody responses to bacteriophage were as severely depressed as in untreated ADA-deficient patients. Treatment with weekly injections of PEG-ADA resulted in normalization of T-cell numbers in all four patients, normal or near-normal T-cell function in two, and mildly but variably improved T-cell function in the other two patients. Quantitatively and qualitatively normal antibody responses to bacteriophage were observed in three of four patients. Assessment of antibody responses to immunization with bacteriophage phi X174 is a useful method to monitor humoral immune function in treated ADA-deficient patients and can be used to estimate when intravenous immunoglobulin (IVIG) prophylaxis may be safely discontinued.

Authors
Ochs, HD; Buckley, RH; Kobayashi, RH; Kobayashi, AL; Sorensen, RU; Douglas, SD; Hamilton, BL; Hershfield, MS
MLA Citation
Ochs, HD, Buckley, RH, Kobayashi, RH, Kobayashi, AL, Sorensen, RU, Douglas, SD, Hamilton, BL, and Hershfield, MS. "Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency." Blood 80.5 (September 1, 1992): 1163-1171.
PMID
1387561
Source
pubmed
Published In
Blood
Volume
80
Issue
5
Publish Date
1992
Start Page
1163
End Page
1171

Mechanism of pokeweed mitogen inhibition of rhIL-4-induced human IgE synthesis.

Pokeweed mitogen (PWM) suppressed rhIL-4-induced IgE synthesis in a concentration-dependent manner. When rhIL-4 was present from Day 0, PWM added to cultures on Day 0 or 3 inhibited MNC IgE synthesis but not when it was added on Day 6 or later. The concentration of interferon-gamma (IFN-gamma) in MNC culture supernatants varied directly with the quantity of PWM added. Conversely, rhIL-4-stimulated MNC culture IgE concentrations varied inversely with the dose of PWM added and the IFN-gamma concentrations induced. The addition of a rabbit polyclonal neutralizing anti-human IFN-gamma antibody to rhIL-4 plus PWM-stimulated cultures partially or completely reversed PWM-induced inhibition of rhIL-4-induced IgE synthesis. PWM failed to inhibit rhIL-4-induced IgE synthesis by isolated B cells cocultured with monocytes and T cells from a clone unable to produce IFN-gamma message or protein. These findings are consistent with the postulate that PWM inhibits rhIL-4-induced IgE synthesis by inducing the production of IFN-gamma.

Authors
Claassen, JL; Levine, AD; Buckley, RH
MLA Citation
Claassen, JL, Levine, AD, and Buckley, RH. "Mechanism of pokeweed mitogen inhibition of rhIL-4-induced human IgE synthesis." Cell Immunol 140.2 (April 1992): 357-369.
PMID
1347486
Source
pubmed
Published In
Cellular Immunology
Volume
140
Issue
2
Publish Date
1992
Start Page
357
End Page
369

Workshop C: The growing importance of clinical immunology: Impact on the allergy training program and the practice of allergy

Authors
Eggleston, PA; Huston, DP; Shearer, WT; Bloch, KJ; Busse, WW; Rich, RR; Bonagura, VR; Buckley, RH; Prez, LD; Grant, JA; Jones, JF; Knutsen, AP; Lockey, RF; Lopez, M; Jr, SRM; McGeady, SJ; Metcalfe, DD; Nel, A; Oleske, JM
MLA Citation
Eggleston, PA, Huston, DP, Shearer, WT, Bloch, KJ, Busse, WW, Rich, RR, Bonagura, VR, Buckley, RH, Prez, LD, Grant, JA, Jones, JF, Knutsen, AP, Lockey, RF, Lopez, M, Jr, SRM, McGeady, SJ, Metcalfe, DD, Nel, A, and Oleske, JM. "Workshop C: The growing importance of clinical immunology: Impact on the allergy training program and the practice of allergy." Journal of Allergy and Clinical Immunology 90.6 I (1992): 999-1001.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
90
Issue
6 I
Publish Date
1992
Start Page
999
End Page
1001
DOI
10.1016/0091-6749(92)90476-I

Diagnostic laboratory immunology: a subspecialty that encompasses clinical as well as laboratory immunology.

Authors
Bloch, KJ; Buckley, RH; Kohler, PF
MLA Citation
Bloch, KJ, Buckley, RH, and Kohler, PF. "Diagnostic laboratory immunology: a subspecialty that encompasses clinical as well as laboratory immunology." J Allergy Clin Immunol 88.6 (December 1991): 961-963.
PMID
1744367
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
88
Issue
6
Publish Date
1991
Start Page
961
End Page
963

Mononuclear cells from patients with the hyper-IgE syndrome produce little IgE when they are stimulated with recombinant human interleukin-4.

To investigate whether B cells from patients with the hyper-IgE syndrome are more sensitive to the effects of interleukin-4 in vitro than B cells of normal or atopic individuals, we stimulated blood mononuclear cells (MNC) with varying doses of recombinant human interleukin 4 (rhIL-4) and measured supernatant IgE concentrations after 18 days of culture. Geometric mean spontaneous IgE synthesis after 18 days of culture without rhIL-4 was low (less than 3 ng/ml) and similar for MNCs from nine patients with the hyper-IgE syndrome, nine atopic and nine normal subjects. As found in our previous studies, MNCs from the nine atopic and the nine normal donors produced significant and similar quantities of IgE (geometric mean maximum IgE, 25.2 and 18.7 ng/ml, respectively) when MNCs were stimulated with rhIL-4. MNCs from both donor groups had similar sensitivity to the concentration of IL-4 eliciting the IgE response. In striking contrast, MNCs from the nine patients with the hyper-IgE syndrome failed to produce significant IgE over that produced spontaneously when MNCs were stimulated by a wide range of rhIL-4 concentrations. Coculture of B cell-enriched subpopulations from patients with the hyper-IgE syndrome with T cell-enriched subpopulations from nonatopic and atopic donors failed to restore responsiveness to rhIL-4. The addition of anti-CD40 monoclonal antibody to MNC cultures did result in enhancement of rhIL-4 IgE synthesis by MNCs from patients with the hyper-IgE syndrome, but the concentration of anti-CD40 required to elicit this enhancement was tenfold higher than for control MNCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Claasen, JJ; Levine, AD; Schiff, SE; Buckley, RH
MLA Citation
Claasen, JJ, Levine, AD, Schiff, SE, and Buckley, RH. "Mononuclear cells from patients with the hyper-IgE syndrome produce little IgE when they are stimulated with recombinant human interleukin-4." J Allergy Clin Immunol 88.5 (November 1991): 713-721.
PMID
1720150
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
88
Issue
5
Publish Date
1991
Start Page
713
End Page
721

Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism

Authors
Friedman, NJ; Shiff, SE; Ward, FE; Schiff, RI; Buckley, RH
MLA Citation
Friedman, NJ, Shiff, SE, Ward, FE, Schiff, RI, and Buckley, RH. "Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism." Pediatric Allergy and Immunology 2.3 (September 1991): 111-116.
Source
crossref
Published In
Pediatric Allergy and Immunology
Volume
2
Issue
3
Publish Date
1991
Start Page
111
End Page
116
DOI
10.1111/j.1399-3038.1991.tb00192.x

Donor type natural killer cells after haploidentical T cell-depleted bone marrow stem cell transplantation in a patient with adenosine deaminase-deficient severe combined immunodeficiency.

T cell-depleted haploidentical (parental) bone marrow stem cell transplants are given to most infants with the syndrome of severe combined immunodeficiency (SCID) because they have no available HLA-identical sibling potential donors. Since they usually do not undergo cytoreduction prior to transplantation, these children later demonstrate mixed hematopoietic chimerism. Most often, T cells (but usually not B lymphocytes, macrophages, or other hematopoietic cells) can be shown to be of donor type. The origin of natural killer (NK) cells in such chimeras has not been reported. Two lymphocyte lines derived from the CD16+ fraction of an adenosine deaminase (ADA)-deficient male SCID's blood mononuclear cells (MNC) 13 months following maternal marrow stem cell transplantation demonstrated typical phenotypic and functional characteristics of NK cells after expansion. Karyotyping showed both lines to be XX. Thus, NK cell engraftment can occur in SCID infants who have not been conditioned, even when significant NK cell function is present before transplantation.

Authors
Gaines, AD; Schiff, SE; Buckley, RH
MLA Citation
Gaines, AD, Schiff, SE, and Buckley, RH. "Donor type natural killer cells after haploidentical T cell-depleted bone marrow stem cell transplantation in a patient with adenosine deaminase-deficient severe combined immunodeficiency." Clin Immunol Immunopathol 60.2 (August 1991): 299-304.
PMID
1712689
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
60
Issue
2
Publish Date
1991
Start Page
299
End Page
304

The use of intravenous immune globulin in immunodeficiency diseases.

Authors
Buckley, RH; Schiff, RI
MLA Citation
Buckley, RH, and Schiff, RI. "The use of intravenous immune globulin in immunodeficiency diseases." N Engl J Med 325.2 (July 11, 1991): 110-117. (Review)
PMID
2052044
Source
pubmed
Published In
The New England journal of medicine
Volume
325
Issue
2
Publish Date
1991
Start Page
110
End Page
117
DOI
10.1056/NEJM199107113250207

Rapid infusion of Sandoglobulin in patients with primary humoral immunodeficiency.

We studied 16 patients with primary disorders of humoral immunity to determine the practicality of infusing intravenous gamma globulin at rates of infusion and concentrations higher than the 4 mg/kg/min and 6% currently recommended. In the first portion of the study, the concentration of Sandoglobulin was increased from 6% to 12%. In the second portion, the flow rate was increased to 5 mg/kg/min, and if no reactions occurred, the time of each successive infusion was decreased by 10 minutes until infusions were completed in 15 to 20 minutes or vasomotor reactions occurred. Thirteen of the 16 patients completed the study; six patients achieved reaction-free rates greater than 15 mg/kg/min, and the other patients achieved rates ranging from 7.1 to 12 mg/kg/min. Seven patients had infusion times less than 30 minutes, with four patients completing infusions in 15 minutes. In the 13 patients who completed the study, there were 14 reactions in 159 infusions, mostly fever and chills, and often at the end or after the infusion. Only one infusion could not be completed because of an adverse reaction. Three patients were not able to complete the study because of adverse reactions; there were seven reactions in 11 infusions in these three patients, although none of the reactions were considered serious. Overall, in this study, most immunodeficient patients (13/16) were able to tolerate infusion rates of Sandoglobulin two to 10 times higher than the standard rates now recommended. The maximal rate of infusion must be individualized, but for carefully selected patients, infusions of 400 mg/kg can be completed in 1 hour or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Schiff, RI; Sedlak, D; Buckley, RH
MLA Citation
Schiff, RI, Sedlak, D, and Buckley, RH. "Rapid infusion of Sandoglobulin in patients with primary humoral immunodeficiency." J Allergy Clin Immunol 88.1 (July 1991): 61-67.
PMID
1906490
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
88
Issue
1
Publish Date
1991
Start Page
61
End Page
67

Antibody responses to protein, polysaccharide, and phi X174 antigens in the hyperimmunoglobulinemia E (hyper-IgE) syndrome.

To investigate whether an underlying defect in antibody (Ab)-forming capacity could contribute to the infection susceptibility of patients with hyper-IgE syndrome, we evaluated 11 such patients for their responses to bacteriophage phi X174 (phi X174), diphtheria and tetanus toxoids, and pneumococcal (Pneumovax) and Hemophilus influenzae vaccines. Three of nine patients immunized with phi X174 had normal primary and secondary Ab responses, five had accelerated declines in their titers after initially normal primary Ab responses and lower than normal secondary Ab responses, and two of the latter patients failed to switch normally from IgM to IgG Ab production. Only one of 10 patients tested had normal Ab responses to diphtheria toxoid, and postimmunization antitetanus titers were abnormally low in five of the 10 patients tested. Serum Abs to H. influenzae polyribose phosphate were protective in seven of the eight immunized patients. Five of the nine patients administered Pneumovax had poor Ab responses to at least one of the pneumococcal serotypes 7, 9, or 14. Abnormal antipolysaccharide responses did not correlate with IgG2 deficiency. All patients responded with protective Ab levels to type 3. Thus, patients with hyper-IgE syndrome are heterogeneous with respect to their Ab-forming capacities. Ab deficiency may contribute to infection susceptibility in some of these patients.

Authors
Sheerin, KA; Buckley, RH
MLA Citation
Sheerin, KA, and Buckley, RH. "Antibody responses to protein, polysaccharide, and phi X174 antigens in the hyperimmunoglobulinemia E (hyper-IgE) syndrome." J Allergy Clin Immunol 87.4 (April 1991): 803-811.
PMID
1826506
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
87
Issue
4
Publish Date
1991
Start Page
803
End Page
811

REDUCED FREQUENCY OF CD45RO+ LYMPHOCYTES-T IN BLOOD OF HYPER IGE SYNDROME PATIENTS

Authors
BUCKLEY, RH; SCHIFF, SE; HAYWARD, AR
MLA Citation
BUCKLEY, RH, SCHIFF, SE, and HAYWARD, AR. "REDUCED FREQUENCY OF CD45RO+ LYMPHOCYTES-T IN BLOOD OF HYPER IGE SYNDROME PATIENTS." FASEB JOURNAL 5.6 (March 19, 1991): A1636-A1636.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
5
Issue
6
Publish Date
1991
Start Page
A1636
End Page
A1636

ANTIBODY-RESPONSES TO BACTERIOPHAGE PHI-X174 IN PATIENTS WITH ADENOSINE-DEAMINASE DEFICIENCY

Authors
OCHS, HD; BUCKLEY, RH; KOBAYASHI, RH; KOBAYASHI, AL; SORENSEN, RU; HERSHFIELD, MS
MLA Citation
OCHS, HD, BUCKLEY, RH, KOBAYASHI, RH, KOBAYASHI, AL, SORENSEN, RU, and HERSHFIELD, MS. "ANTIBODY-RESPONSES TO BACTERIOPHAGE PHI-X174 IN PATIENTS WITH ADENOSINE-DEAMINASE DEFICIENCY." February 1991.
Source
wos-lite
Published In
Clinical Research
Volume
39
Issue
1
Publish Date
1991
Start Page
A57
End Page
A57

The use of intravenous immune globulin in immunodeficiency diseases

Authors
Buckley, RH; Schiff, RI
MLA Citation
Buckley, RH, and Schiff, RI. "The use of intravenous immune globulin in immunodeficiency diseases." New England Journal of Medicine 325.2 (1991): 110-117.
Source
scival
Published In
New England Journal of Medicine
Volume
325
Issue
2
Publish Date
1991
Start Page
110
End Page
117

Prevalence of lymphocytopenia in severe combined immunodeficiency.

Authors
Gossage, DL; Buckley, RH
MLA Citation
Gossage, DL, and Buckley, RH. "Prevalence of lymphocytopenia in severe combined immunodeficiency." N Engl J Med 323.20 (November 15, 1990): 1422-1423. (Letter)
PMID
2233913
Source
pubmed
Published In
The New England journal of medicine
Volume
323
Issue
20
Publish Date
1990
Start Page
1422
End Page
1423
DOI
10.1056/NEJM199011153232014

X-linked severe combined immunodeficiency. Diagnosis in males with sporadic severe combined immunodeficiency and clarification of clinical findings.

Over 80% of infants with severe combined immunodeficiency (SCID) of unknown genetic etiology are males, yet less than a third of these affected males have a family history of X-linked disease. To help identify new mutations of the X-linked SCID gene and to provide genetic counseling, X chromosome inactivation patterns in T cells from 16 women who had sons with sporadic SCID were examined. Between 9 and 35 human/hamster hybrids that selectively retained the active human X chromosome were produced from the T cells of each woman and analyzed with an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. Exclusive use of a single X as the active X was seen in the T cell hybrids from 7 of the 16 women, identifying these women as carriers of X-linked SCID. Studies on additional family members confirmed the mutant nature of the inactive X and revealed the source of the new mutation in three families. To determine whether there were any laboratory characteristics that might differentiate the boys whose mothers were identified as carriers of X-linked SCID from those whose mothers were not, the clinical records of both groups were compared to each other and to a group of 14 boys with a family history of X-linked SCID. The most consistent finding in the 21 patients with X-linked SCID was an elevated proportion of B cells. These data demonstrate the high incidence of spontaneous mutation for the X-linked SCID gene and help clarify the characteristic presenting features of this disorder.

Authors
Conley, ME; Buckley, RH; Hong, R; Guerra-Hanson, C; Roifman, CM; Brochstein, JA; Pahwa, S; Puck, JM
MLA Citation
Conley, ME, Buckley, RH, Hong, R, Guerra-Hanson, C, Roifman, CM, Brochstein, JA, Pahwa, S, and Puck, JM. "X-linked severe combined immunodeficiency. Diagnosis in males with sporadic severe combined immunodeficiency and clarification of clinical findings." J Clin Invest 85.5 (May 1990): 1548-1554.
PMID
2332505
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
85
Issue
5
Publish Date
1990
Start Page
1548
End Page
1554
DOI
10.1172/JCI114603

Prenatal test for X-linked severe combined immunodeficiency by analysis of maternal X-chromosome inactivation and linkage analysis.

Authors
Puck, JM; Krauss, CM; Puck, SM; Buckley, RH; Conley, ME
MLA Citation
Puck, JM, Krauss, CM, Puck, SM, Buckley, RH, and Conley, ME. "Prenatal test for X-linked severe combined immunodeficiency by analysis of maternal X-chromosome inactivation and linkage analysis." N Engl J Med 322.15 (April 12, 1990): 1063-1066.
PMID
2320067
Source
pubmed
Published In
The New England journal of medicine
Volume
322
Issue
15
Publish Date
1990
Start Page
1063
End Page
1066
DOI
10.1056/NEJM199004123221508

Recombinant human IL-4 induces IgE and IgG synthesis by normal and atopic donor mononuclear cells. Similar dose response, time course, requirement for T cells, and effect of pokeweed mitogen.

Unfractionated human blood mononuclear cells (MNC) from normal and atopic donors cultured in enriched Iscove's modified Dulbecco's medium supplemented with 10% FCS responded similarly to stimulation with purified human rIL-4 (rhIL-4) with respect to the concentration required to induce IgE synthesis and the magnitude and kinetics of the IgE response. The IgE response of MNC was IL-4 dose-dependent, increasing linearly with IL-4 concentrations between 0.2 and 2.5 ng/ml and plateauing at concentrations of 5 ng/ml or more. rhIL-4-induced IgE synthesis was first detected at 9 days after stimulation and supernatant IgE concentrations reached a maximum on day 18. rhIL-4 stimulated IgE synthesis by MNC from all donors tested, with peak supernatant IgE concentrations ranging from 3 to 372 ng/ml. The nonatopic group (n = 15) geometric mean peak concentration was 24.0 ng/ml and that of the atopic group (n = 19) was 20.0 ng/ml (p = NS). rhIL-4 also stimulated IgG synthesis by MNC from some (but not all) donors in quantities comparable to those induced by PWM. Maximum supernatant IgG concentrations in responders were found 18 days after stimulation. When PWM was added to the IL-4-stimulated cultures, it completely inhibited rhIL-4-induced IgE and IgG synthesis. rhIL-4 also completely inhibited PWM-induced IgG synthesis. Stimulation of IgE synthesis by rhIL-4 required the presence of T cells. T cell clone supernatants did not support rhIL-4-induced IgE synthesis by B cells. T cells from atopic and nonatopic donors restored rhIL-4-stimulated IgE synthesis by B cells from either source to a similar extent.

Authors
Claassen, JL; Levine, AD; Buckley, RH
MLA Citation
Claassen, JL, Levine, AD, and Buckley, RH. "Recombinant human IL-4 induces IgE and IgG synthesis by normal and atopic donor mononuclear cells. Similar dose response, time course, requirement for T cells, and effect of pokeweed mitogen." J Immunol 144.6 (March 15, 1990): 2123-2130.
PMID
2313090
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
144
Issue
6
Publish Date
1990
Start Page
2123
End Page
2130

Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency.

We have identified five patients with severe combined immunodeficiency (SCID) who developed multiple monoclonal serum immunoglobulin components (multiclonal gammopathy) following bone marrow transplantation. Four patients received haploidentical bone marrow stem cells depleted of T cells and other mature marrow cells by soy lectin agglutination and/or sheep erythrocyte rosetting. One patient received unfractionated HLA-identical bone marrow. Twenty-one distinct paraproteins were detected: 14 IgG, 5 IgM, and 2 IgA, all containing either kappa or lambda light chains. In the haploidentical stem-cell recipients, these monoclonal immunoglobulins appeared immediately prior to, or concomitant with, a rise in T-cell numbers and function. Resolution or diminution of this multiclonal gammopathy occurred as T-cell function was established. Posttransplant karyotypic analyses revealed PHA-stimulated T cells to be of donor origin in all patients. Karyotyping of B-cell lines posttransplantation revealed them to be 100% donor in the patient receiving unfractionated HLA-identical marrow and 100% host (1/4), 100% donor (1/4), mixed (1/4), or not tested (1/4) in the patients receiving haploidentical marrow stem cells. There was no evidence of Epstein-Barr virus (EBV) infection in any of the patients. All patients are currently alive and well. Immunoglobulin synthesis is normal in the patient who received the HLA-identical marrow but remains below normal in the four patients who received T cell-depleted haploidentical stem cells. The posttransplantation development of monoclonal immunoglobulins in the absence of EBV infection did not adversely affect the outcome of either HLA-identical marrow or haploidentical stem-cell grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Kent, EF; Crawford, J; Cohen, HJ; Buckley, RH
MLA Citation
Kent, EF, Crawford, J, Cohen, HJ, and Buckley, RH. "Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency." J Clin Immunol 10.2 (March 1990): 106-114.
PMID
2338452
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
10
Issue
2
Publish Date
1990
Start Page
106
End Page
114

A cell culture system that enhances mononuclear cell IgE synthesis induced by recombinant human interleukin-4.

A new culture system is described in which recombinant human interleukin-4 (rhIL-4) consistently induces the synthesis of large quantities of IgE by human blood mononuclear cells (MNC). Unfractionated MNC were cultured in complete Iscove's modified Dulbecco's medium (C-IMDM), composed of IMDM enriched with human transferrin, bovine insulin, bovine serum albumin, oleic acid, palmitic acid, linoleic acid, and fetal calf serum (FCS). Under these culture conditions, MNC from four donors synthesized mean quantities of IgE of 76 ng/ml at plateau after stimulation with rhIL-4 in concentrations ranging from 0.04 to 80 ng/ml (plateau rhIL-4 concentrations were 5 ng/ml or greater). In contrast, rhIL-4 failed to induce significant IgE synthesis at any of those doses of rhIL-4 in parallel MNC cultures performed in RPMI 1640 supplemented with FCS (RPMI 1640). Additional optimal conditions for the induction of IgE synthesis in this system were a MNC concentration of 1-2 X 10(6)/ml and a culture time of 18 days. Variability was noted in the amount of IgE produced by different donors (CV 0.22) and by the same donor when tested on different occasions (mean CV 0.21), but no donor's MNC failed to produce significant IgE in response to rhIL-4 when cultured in C-IMDM. The geometric mean IgE production induced by optimal IL-4 concentrations for the entire group of 16 subjects was 36.8 ng/ml IgE, with the lowest day 18 mean IgE concentration for any donor being 10.6 ng/ml and the highest 372.2 ng/ml. The enhanced rhIL-4-induced IgE synthesis supported by C-IMDM was due to the combined effects of the added enrichment factors and not to differences in the viabilities of MNC cultured in C-IMDM and RPMI 1640. This culture system will alleviate the problems of inconsistent and low quantities of IgE induced by IL-4 that confound most current culture systems used to examine rhIL-4-induced IgE synthesis. It will, thereby, facilitate further investigation of the regulation of human IgE synthesis.

Authors
Claassen, JL; Levine, AD; Buckley, RH
MLA Citation
Claassen, JL, Levine, AD, and Buckley, RH. "A cell culture system that enhances mononuclear cell IgE synthesis induced by recombinant human interleukin-4." J Immunol Methods 126.2 (February 9, 1990): 213-222.
PMID
2303731
Source
pubmed
Published In
Journal of Immunological Methods
Volume
126
Issue
2
Publish Date
1990
Start Page
213
End Page
222

Modified MHC restriction of donor-origin T cells in humans with severe combined immunodeficiency transplanted with haploidentical bone marrow stem cells.

The choice of class II MHC determinants that serve as self-recognition elements for murine CD4+ T cells is thought to be determined by the environment in which T cells mature rather than their genotype. Patients with severe combined immunodeficiency (SCID) reconstituted with T cell depleted haploidentical parental stem cells provide an excellent model for studying this phenomenon in humans. After engraftment, the T cells that develop in these infants are all of donor origin. We sought to determine whether the successful immune reconstitution observed in two such SCID chimeras involved modification of the MHC restriction of Ag recognition by the genetically donor T cells as they matured to become competent T cells in the infants' microenvironment. A tetanus toxoid (TT)-specific T cell line and TT-specific T cell clones were established from the blood of two reconstituted SCID patients and from their maternal donors. T cell responsiveness was determined by [3H]thymidine incorporation after TT presentation by EBV-transformed B cell lines (EBV-B) from various donors. The TT-specific T cell line from patient 1 proliferated when presented Ag by patient, maternal donor, and paternal APC. A CD4+ donor origin clone that proliferated when presented TT by patient and paternal EBV-B, but not by maternal donor EBV-B, was isolated from each patient. TT recognition by these clones was shown to be restricted by the HLA DR determinant shared by patient and father, but not present in the donor. Four TT-specific clones isolated from maternal donors failed to proliferate when presented TT by the appropriate paternal EBV-B. These studies demonstrate that, in these human SCID bone marrow chimeras, engrafted donor-origin stem cells maturing to competent T cells in the recipient microenvironment are capable of utilizing recipient HLA determinants as restriction elements for Ag recognition. This suggests that human, as well as murine, MHC restriction patterns for Ag recognition by CD4+ T cells are environmentally determined.

Authors
Roberts, JL; Volkman, DJ; Buckley, RH
MLA Citation
Roberts, JL, Volkman, DJ, and Buckley, RH. "Modified MHC restriction of donor-origin T cells in humans with severe combined immunodeficiency transplanted with haploidentical bone marrow stem cells." J Immunol 143.5 (September 1, 1989): 1575-1579.
PMID
2474604
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
143
Issue
5
Publish Date
1989
Start Page
1575
End Page
1579

Impaired antibody response to polysaccharides in association with functional asplenia.

Authors
Gaines, AD; Buckley, RH
MLA Citation
Gaines, AD, and Buckley, RH. "Impaired antibody response to polysaccharides in association with functional asplenia." J Pediatr 114.1 (January 1989): 89-91.
PMID
2909710
Source
pubmed
Published In
The Journal of Pediatrics
Volume
114
Issue
1
Publish Date
1989
Start Page
89
End Page
91

Accelerated development of immunity following transplantation of maternal marrow stem cells into infants with severe combined immunodeficiency and transplacentally acquired lymphoid chimerism.

Transplacentally acquired lymphoid chimerism was detected in two infants with severe combined immunodeficiency (SCID) by two-colour cytofluorographic studies. These cells had no demonstrable function in studies in vitro. Following T cell-depleted maternal bone marrow stem cell transplantation, evidence of T cell function was detected 20 and 50 days later, and transient B cell function was detected 50 days later. These immune functions appeared much sooner than the 90-120 days usually required for T cell function and the 2-2.5 years for B cell function to develop after haplo-identical stem cell transplants into SCID infants without transplacental engraftment. The presence of maternal lymphoid chimerism did not interfere with haplo-identical marrow cell engraftment, even though no pre-transplant immunosuppression was given. This observation suggests that the transplanted maternal marrow stem cell in some way conferred reactivity on the engrafted but apparently non-functional mature T cells that had entered the fetal circulation transplacentally.

Authors
Barrett, MJ; Buckley, RH; Schiff, SE; Kidd, PC; Ward, FE
MLA Citation
Barrett, MJ, Buckley, RH, Schiff, SE, Kidd, PC, and Ward, FE. "Accelerated development of immunity following transplantation of maternal marrow stem cells into infants with severe combined immunodeficiency and transplacentally acquired lymphoid chimerism." Clin Exp Immunol 72.1 (April 1988): 118-123.
PMID
3293848
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
72
Issue
1
Publish Date
1988
Start Page
118
End Page
123

MODIFIED T-CELL MHC RESTRICTION FOLLOWING SUCCESSFUL HAPLOIDENTICAL BONE-MARROW STEM-CELL TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID)

Authors
ROBERTS, JL; VOLKMAN, DJ; BUCKLEY, RH
MLA Citation
ROBERTS, JL, VOLKMAN, DJ, and BUCKLEY, RH. "MODIFIED T-CELL MHC RESTRICTION FOLLOWING SUCCESSFUL HAPLOIDENTICAL BONE-MARROW STEM-CELL TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID)." FASEB JOURNAL 2.4 (March 15, 1988): A448-A448.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
2
Issue
4
Publish Date
1988
Start Page
A448
End Page
A448

Certification in diagnostic laboratory immunology.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Certification in diagnostic laboratory immunology." Ann Intern Med 108.3 (March 1988): 458-459.
PMID
3341676
Source
pubmed
Published In
Annals of internal medicine
Volume
108
Issue
3
Publish Date
1988
Start Page
458
End Page
459

Immune Thrombocytopenia Treated with High-Dose Intravenous Gamma Globulin and Corticosteroids in Two Patients with Wiskott-Aldrich Syndrome

Authors
MINGS, RONALD; WILLIAMS, LARRYW; KNUTSEN, ALANP; WARREN, ROBERTW; BUCKLEY, REBECCAH
MLA Citation
MINGS, RONALD, WILLIAMS, LARRYW, KNUTSEN, ALANP, WARREN, ROBERTW, and BUCKLEY, REBECCAH. "Immune Thrombocytopenia Treated with High-Dose Intravenous Gamma Globulin and Corticosteroids in Two Patients with Wiskott-Aldrich Syndrome." Pediatric Asthma, Allergy & Immunology 2.3 (January 1988): 191-197.
Source
crossref
Published In
Pediatric Asthma, Allergy & Immunology
Volume
2
Issue
3
Publish Date
1988
Start Page
191
End Page
197
DOI
10.1089/pai.1988.2.191

ANTIGEN-SPECIFIC HUMORAL AND CELLULAR IMMUNE-RESPONSES DURING TREATMENT OF ADENOSINE-DEAMINASE DEFICIENT SEVERE COMBINED IMMUNODEFICIENCY (ADA-SCID) WITH POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)

Authors
CLAASSEN, JL; KOBAYASHI, RH; KOBAYASHI, AL; HERSHFIELD, MS; SCHIFF, RI; BUCKLEY, RH
MLA Citation
CLAASSEN, JL, KOBAYASHI, RH, KOBAYASHI, AL, HERSHFIELD, MS, SCHIFF, RI, and BUCKLEY, RH. "ANTIGEN-SPECIFIC HUMORAL AND CELLULAR IMMUNE-RESPONSES DURING TREATMENT OF ADENOSINE-DEAMINASE DEFICIENT SEVERE COMBINED IMMUNODEFICIENCY (ADA-SCID) WITH POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)." January 1988.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
81
Issue
1
Publish Date
1988
Start Page
237
End Page
237
DOI
10.1016/0091-6749(88)90510-6

Food Allergy

Authors
Sampson, H; Buckley, RH; Metcalfe, DD
MLA Citation
Sampson, H, Buckley, RH, and Metcalfe, DD. "Food Allergy." JAMA: The Journal of the American Medical Association 258.20 (November 27, 1987): 2886-2890.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
258
Issue
20
Publish Date
1987
Start Page
2886
End Page
2890
DOI
10.1001/jama.1987.03400200092010

Allergic Skin Disorders

Authors
Kaplan, AP; Buckley, RH; Mathews, KP
MLA Citation
Kaplan, AP, Buckley, RH, and Mathews, KP. "Allergic Skin Disorders." JAMA: The Journal of the American Medical Association 258.20 (November 27, 1987): 2900-2909.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
258
Issue
20
Publish Date
1987
Start Page
2900
End Page
2909
DOI
10.1001/jama.1987.03400200106012

Food allergy.

Authors
Sampson, HA; Buckley, RH; Metcalfe, DD
MLA Citation
Sampson, HA, Buckley, RH, and Metcalfe, DD. "Food allergy." JAMA 258.20 (November 27, 1987): 2886-2890. (Review)
PMID
3312671
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
258
Issue
20
Publish Date
1987
Start Page
2886
End Page
2890

Allergic skin disorders.

Authors
Kaplan, AP; Buckley, RH; Mathews, KP
MLA Citation
Kaplan, AP, Buckley, RH, and Mathews, KP. "Allergic skin disorders." JAMA 258.20 (November 27, 1987): 2900-2909. (Review)
PMID
3312673
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
258
Issue
20
Publish Date
1987
Start Page
2900
End Page
2909

Immunodeficiency diseases.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Immunodeficiency diseases." JAMA 258.20 (November 27, 1987): 2841-2850. (Review)
PMID
3312668
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
258
Issue
20
Publish Date
1987
Start Page
2841
End Page
2850

Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients.

The courses of six patients with adenosine deaminase (ADA) and two with purine nucleoside phosphorylase (PNP) deficiencies were evaluated before and after therapy. The heterogeneity of immunologic and clinical parameters was striking in each enzyme deficiency. In both PNP and ADA deficiency, some patients had very low immunoglobulin levels, while others had normal levels. T-cell function was always low in patients with ADA deficiency. In the two patients with PNP deficiency, contrary to the classical descriptions of this disorder, T-cell function fluctuated with time. Five ADA-deficient patients were treated with irradiated normal red-cell transfusions as a form of enzyme replacement and showed no lasting benefit. Three of the ADA-deficient patients and one of the PNP-deficient patients were given transplants of haploidentical parental bone marrow stem cells without pretransplant immunosuppression. In the PNP-deficient patient, chimerism has not been documented on enzymatic testing. One ADA-deficient patient has demonstrated long-term engraftment with good B- and T-cell function. Haploidentical bone marrow transplantation is currently the preferred therapy for enzyme-deficient patients with absent T-cell function who do not have an HLA-identical donor, as it may result in a lasting reconstitution of immune function. In those patients with unsatisfactory responses to transplantation, however, specific enzyme replacement or gene therapy may be considered in the future.

Authors
Markert, ML; Hershfield, MS; Schiff, RI; Buckley, RH
MLA Citation
Markert, ML, Hershfield, MS, Schiff, RI, and Buckley, RH. "Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients." J Clin Immunol 7.5 (September 1987): 389-399.
PMID
3116034
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
7
Issue
5
Publish Date
1987
Start Page
389
End Page
399

Pulmonary coin lesion caused by Neisseria mucosa in a child with chronic granulomatous disease.

Authors
Claassen, JL; Eppes, SC; Buckley, RH
MLA Citation
Claassen, JL, Eppes, SC, and Buckley, RH. "Pulmonary coin lesion caused by Neisseria mucosa in a child with chronic granulomatous disease." Pediatr Infect Dis J 6.6 (June 1987): 567-569.
PMID
3615070
Source
pubmed
Published In
Pediatric Infectious Disease Journal
Volume
6
Issue
6
Publish Date
1987
Start Page
567
End Page
569

Studies of human bone marrow treated with soybean lectin and sheep erythrocytes: stepwise analysis of cell morphology, phenotype and function.

Morphological, phenotypic and functional analyses were made of cells obtained at each step after successive treatments of 23 separate human bone marrow suspensions with soybean lectin and sheep erythrocytes (SRBC). The average total number of nucleated cells harvested was 1.9 X 10(10) and the final cell suspensions contained a mean of 1.9 X 10(9) nucleated cells or 9.2 +/- 4.8% of the initial counts. Monoclonal antibody analyses revealed that both T and B lymphocytes were present in every cell fraction in percentages similar to those found initially until after the first SRBC rosette-depletion. Moreover, both soy lectin agglutinated and non-agglutinated cells exhibited vigorous proliferative responses to phytohaemagglutinin and allogeneic cells. Following the SRBC depletions, no cells having T lymphocyte phenotypes or functions could be detected, whereas 5% of the cells reacted with a monoclonal antibody to B lymphocytes. The final fraction was composed predominantly of immature myeloid cells and blasts and was depleted of erythroid elements, lymphocytes and essentially all mature cells. It contained cells reactive with monoclonal antibodies recognizing undifferentiated T cell precursors (3A1), the transferrin receptor (5E9), and a human progenitor cell antigen (My-10). The final fraction was also enriched 10-100-fold for CFU-C and 5-10-fold for CFU-GEMN colonies. These studies fail to demonstrate selective removal of T lymphocytes from human bone marrow cells by soybean lectin agglutination.

Authors
Schiff, SE; Kurtzberg, J; Buckley, RH
MLA Citation
Schiff, SE, Kurtzberg, J, and Buckley, RH. "Studies of human bone marrow treated with soybean lectin and sheep erythrocytes: stepwise analysis of cell morphology, phenotype and function." Clin Exp Immunol 68.3 (June 1987): 685-693.
PMID
3498584
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
68
Issue
3
Publish Date
1987
Start Page
685
End Page
693

Identification of a deletion in the adenosine deaminase gene in a child with severe combined immunodeficiency.

A patient with adenosine deaminase-deficient severe combined immunodeficiency is described whose defect is secondary to deletion of a portion of the ADA structural gene. In Southern analyses, DNA from this patient does not hybridize to a genomic probe that includes the 3' end of exon 1. This implies that both his parents are heterozygous for deletions of exon 1 sequences. Consistent with this finding, the patient has no detectable adenosine deaminase mRNA by Northern analysis. This is the first report of a deletion mutation as the cause of adenosine deaminase deficiency.

Authors
Markert, ML; Hershfield, MS; Wiginton, DA; States, JC; Ward, FE; Bigner, SH; Buckley, RH; Kaufman, RE; Hutton, JJ
MLA Citation
Markert, ML, Hershfield, MS, Wiginton, DA, States, JC, Ward, FE, Bigner, SH, Buckley, RH, Kaufman, RE, and Hutton, JJ. "Identification of a deletion in the adenosine deaminase gene in a child with severe combined immunodeficiency." J Immunol 138.10 (May 15, 1987): 3203-3206.
PMID
3571974
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
138
Issue
10
Publish Date
1987
Start Page
3203
End Page
3206

Advances in the correction of immunodeficiency by bone marrow transplantation.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Advances in the correction of immunodeficiency by bone marrow transplantation." Pediatr Ann 16.5 (May 1987): 412-421.
PMID
3302890
Source
pubmed
Published In
Pediatric annals
Volume
16
Issue
5
Publish Date
1987
Start Page
412
End Page
421

Modified responses to recipient and donor B cells by genetically donor T cells from human haploidentical bone marrow chimeras.

After administration of haploidentical stem cells to infants with severe combined immunodeficiency disease (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-vs-host disease (GVHD). To investigate the effect of the host microenvironment on these genetically donor T cells, mixed leukocyte cultures were carried out. Unfractionated mononuclear cells (MNC) from eight infants with SCID immunologically reconstituted by haploidentical bone marrow stem cells responded in the same pattern as MNC from non-chimeric individuals to autologous and allogeneic irradiated MNC, even though they contained all genetically donor T cells and all genetically patient B cells and monocytes. This included surprisingly vigorous proliferative responses of the patients' MNC to the original donors' irradiated MNC. This autoreactivity could be detected as soon as T cell function appeared post-transplantation and appeared to increase with time. It could be blocked by the addition of monoclonal antibodies to HLA Class II antigens. Responses of most patients' MNC were similar whether stimulated by irradiated MNC from the donor or non-donor parent or by those from unrelated normal controls. Purified genetically donor T cells that had matured from stem cells in the patient's microenvironment responded vigorously to purified donor B cells. These same cells responded much less to patient B cells. In six cases, such genetically donor T cells responded less to patient B cells than fresh donor T cells did to donor B cells in the autologous mixed leukocyte response. By contrast, T cells of donor karyotype from three of the patients responded more vigorously to donor B cells than fresh donor T cells did. Thus, genetically donor T lymphocytes that had matured from stem cells in the recipient microenvironment behaved differently from those that had matured in the donor. The hyporesponsiveness of genetically donor T cells from the patient to patient B cells does not appear to be due to T suppressor cells.

Authors
Schiff, SE; Buckley, RH
MLA Citation
Schiff, SE, and Buckley, RH. "Modified responses to recipient and donor B cells by genetically donor T cells from human haploidentical bone marrow chimeras." J Immunol 138.7 (April 1, 1987): 2088-2094.
PMID
2881966
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
138
Issue
7
Publish Date
1987
Start Page
2088
End Page
2094

TREATMENT OF ADENOSINE-DEAMINASE DEFICIENCY WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE (PEG-ADA)

Authors
HERSHFIELD, MS; BUCKLEY, RH; GREENBERG, ML; MELTON, AL; KOBAYASHI, RH; KOBAYASHI, AL; SCHIFF, R; KURTZBERG, J; MARKERT, ML; ABUCHOWSKI, A
MLA Citation
HERSHFIELD, MS, BUCKLEY, RH, GREENBERG, ML, MELTON, AL, KOBAYASHI, RH, KOBAYASHI, AL, SCHIFF, R, KURTZBERG, J, MARKERT, ML, and ABUCHOWSKI, A. "TREATMENT OF ADENOSINE-DEAMINASE DEFICIENCY WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE (PEG-ADA)." April 1987.
Source
wos-lite
Published In
Clinical Research
Volume
35
Issue
3
Publish Date
1987
Start Page
A593
End Page
A593

Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.

Authors
Hershfield, MS; Buckley, RH; Greenberg, ML; Melton, AL; Schiff, R; Hatem, C; Kurtzberg, J; Markert, ML; Kobayashi, RH; Kobayashi, AL
MLA Citation
Hershfield, MS, Buckley, RH, Greenberg, ML, Melton, AL, Schiff, R, Hatem, C, Kurtzberg, J, Markert, ML, Kobayashi, RH, and Kobayashi, AL. "Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase." N Engl J Med 316.10 (March 5, 1987): 589-596.
PMID
3807953
Source
pubmed
Published In
The New England journal of medicine
Volume
316
Issue
10
Publish Date
1987
Start Page
589
End Page
596
DOI
10.1056/NEJM198703053161005

DEVELOPMENT OF IMMUNITY IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) WITH TRANSPLACENTALLY ACQUIRED MATERNAL LYMPHOCYTES FOLLOWING TRANSPLANTATION OF T-DEPLETED MATERNAL STEM-CELLS

Authors
BARRETT, MJ; SCHIFF, SE; KIDD, PC; BUCKLEY, RH
MLA Citation
BARRETT, MJ, SCHIFF, SE, KIDD, PC, and BUCKLEY, RH. "DEVELOPMENT OF IMMUNITY IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) WITH TRANSPLACENTALLY ACQUIRED MATERNAL LYMPHOCYTES FOLLOWING TRANSPLANTATION OF T-DEPLETED MATERNAL STEM-CELLS." FEDERATION PROCEEDINGS 46.3 (March 1, 1987): 1022-1022.
Source
wos-lite
Published In
The FASEB Journal
Volume
46
Issue
3
Publish Date
1987
Start Page
1022
End Page
1022

DEVELOPMENT OF B-CELL FUNCTION IN HUMAN HAPLOIDENTICAL BONE-MARROW CHIMERAS

Authors
BUCKLEY, RH; OCHS, HD
MLA Citation
BUCKLEY, RH, and OCHS, HD. "DEVELOPMENT OF B-CELL FUNCTION IN HUMAN HAPLOIDENTICAL BONE-MARROW CHIMERAS." FEDERATION PROCEEDINGS 46.3 (March 1, 1987): 1021-1021.
Source
wos-lite
Published In
The FASEB Journal
Volume
46
Issue
3
Publish Date
1987
Start Page
1021
End Page
1021

Successful treatment of autoimmune hemolytic anemia in common variable immunodeficiency with high-dose intravenous gamma globulin.

A patient with common variable immunodeficiency and autoimmune hemolytic anemia was given high-dose (450 mg/kg) intravenous gamma globulin (Sandoglobulin) for five days, followed by single doses of 100 to 200 mg/kg at four-week intervals or whenever the hemoglobin level and hematocrit fell or the reticulocyte count increased. This treatment was accompanied by a stabilization of hematopoietic parameters and reversal of Coombs' positivity, which have been sustained for 34 months. The use of high-dose gamma globulin for autoimmune hemolytic anemia can eliminate the need for other therapeutic modalities that may be detrimental to an immunocompromised host.

Authors
Leickly, FE; Buckley, RH
MLA Citation
Leickly, FE, and Buckley, RH. "Successful treatment of autoimmune hemolytic anemia in common variable immunodeficiency with high-dose intravenous gamma globulin." Am J Med 82.1 (January 1987): 159-162.
PMID
3799677
Source
pubmed
Published In
The American Journal of Medicine
Volume
82
Issue
1
Publish Date
1987
Start Page
159
End Page
162

Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies.

Sera from three hundred five patients with immunoglobulin deficiencies were analyzed for the presence of anti-IgA antibodies by using indirect agglutination and enzyme-linked immunosorbent assay (ELISA). Anti-IgA antibodies were observed in 15 of 68 (22%) patients with hypogammaglobulinemia and 53 of 185 (29%) patients with selective IgA deficiency, both groups having serum IgA less than 0.05 g/liter. The highest frequency, 6 of 10 or 60%, was noted for patients with a combined IgA-IgG2 deficiency. No anti-IgA antibodies were detected in 25 patients with serum IgA between 0.05 and 0.27 g/liter and normal amounts of serum IgM and IgG or in 17 patients with hypogammaglobulinemia who had serum IgA of 0.05-0.7 g/liter. The anti-IgA antibodies were primarily of the IgG class, but IgD and IgM anti-IgA were occasionally found. IgE anti-IgA antibodies could not be detected with the presently used technique. The IgG anti-IgA antibodies were mainly of the IgG1 subclass but occasionally also of the subclasses IgG2, IgG3, and IgG4. Of eight patients with anti-IgA antibodies, seven tolerated Ig prophylaxis with a commercial immunoglobulin preparation low in IgA when given either intramuscularly or intravenously. The titers of anti-IgA in the sera of these patients did not rise in relation to the prophylaxis. Only one of the eight patients had a history of previous anaphylactic reactions to IgA-containing blood products. He tolerated six Ig infusions during 5 months with the IgA-depleted preparation without any adverse effects but showed increasing levels of anti-IgA antibodies and ultimately experienced a near-fatal reaction at the seventh infusion.

Authors
Björkander, J; Hammarström, L; Smith, CI; Buckley, RH; Cunningham-Rundles, C; Hanson, LA
MLA Citation
Björkander, J, Hammarström, L, Smith, CI, Buckley, RH, Cunningham-Rundles, C, and Hanson, LA. "Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies." J Clin Immunol 7.1 (January 1987): 8-15.
PMID
3494039
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
7
Issue
1
Publish Date
1987
Start Page
8
End Page
15

TREATMENT OF ADENOSINE DEAMINASE-DEFICIENT SEVERE COMBINED IMMUNE-DEFICIENCY (ADA-SCID) WITH POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)

Authors
MELTON, A; HERSHFIELD, MS; GREENBERG, ML; HATEM, C; MARKERT, ML; KURTZBERG, J; ABUCHOWSKI, A; BUCKLEY, RH
MLA Citation
MELTON, A, HERSHFIELD, MS, GREENBERG, ML, HATEM, C, MARKERT, ML, KURTZBERG, J, ABUCHOWSKI, A, and BUCKLEY, RH. "TREATMENT OF ADENOSINE DEAMINASE-DEFICIENT SEVERE COMBINED IMMUNE-DEFICIENCY (ADA-SCID) WITH POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)." January 1987.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
79
Issue
1
Publish Date
1987
Start Page
252
End Page
252

Natural-killer-cell function and bone marrow transplantation.

Authors
Markert, ML; Buckley, RH
MLA Citation
Markert, ML, and Buckley, RH. "Natural-killer-cell function and bone marrow transplantation." N Engl J Med 315.22 (November 27, 1986): 1418-1419. (Letter)
PMID
3534572
Source
pubmed
Published In
The New England journal of medicine
Volume
315
Issue
22
Publish Date
1986
Start Page
1418
End Page
1419
DOI
10.1056/NEJM198611273152216

Expression of the gene defect in X-linked agammaglobulinemia.

Authors
Conley, ME; Brown, P; Pickard, AR; Buckley, RH; Miller, DS; Raskind, WH; Singer, JW; Fialkow, PJ
MLA Citation
Conley, ME, Brown, P, Pickard, AR, Buckley, RH, Miller, DS, Raskind, WH, Singer, JW, and Fialkow, PJ. "Expression of the gene defect in X-linked agammaglobulinemia." N Engl J Med 315.9 (August 28, 1986): 564-567.
PMID
3488506
Source
pubmed
Published In
The New England journal of medicine
Volume
315
Issue
9
Publish Date
1986
Start Page
564
End Page
567
DOI
10.1056/NEJM198608283150907

ANAPHYLAXIS AFTER ADMINISTRATION OF GAMMA-GLOBULIN FOR HYPOGAMMAGLOBULINEMIA - REPLY

Authors
BURKS, AW; SAMPSON, HA; BUCKLEY, RH
MLA Citation
BURKS, AW, SAMPSON, HA, and BUCKLEY, RH. "ANAPHYLAXIS AFTER ADMINISTRATION OF GAMMA-GLOBULIN FOR HYPOGAMMAGLOBULINEMIA - REPLY." NEW ENGLAND JOURNAL OF MEDICINE 315.8 (August 21, 1986): 520-520.
Source
wos-lite
Published In
The New England journal of medicine
Volume
315
Issue
8
Publish Date
1986
Start Page
520
End Page
520

Anaphylaxis after administration of gamma globulin for hypogammaglobulinemia.

MLA Citation
"Anaphylaxis after administration of gamma globulin for hypogammaglobulinemia." The New England journal of medicine 315.8 (August 1986): 519-520. (Letter)
PMID
2426594
Source
epmc
Published In
The New England journal of medicine
Volume
315
Issue
8
Publish Date
1986
Start Page
519
End Page
520

Humoral immunodeficiency.

Humoral (or antibody) immunodeficiency syndromes may occur as apparent congenital or acquired abnormalities, with deficiencies in all or in only some classes of immunoglobulins. Most patients are recognized because of recurrent infections with high-grade extracellular encapsulated bacterial pathogens, but some with selective IgA deficiency or with transient hypogammaglobulinemia of infancy may have few or no infections. Although general population statistics are not available, most defects are thought to be rare; humoral immunodeficiency is more prevalent than cellular immunodeficiency, possibly due to early death from the latter defects. Disorders affecting B-cell function may be inherited as X-linked recessive or as autosomal traits. Although considerable information exists about such defects at a functional and cellular level, the primary biologic errors are as yet unknown for all of them. Apparent abnormalities of B-cell maturation and/or intrinsic B-cell malfunction are seen in a majority of these defects. The heterogeneity of B-cell morphology and function in large pedigrees of patients with X-linked agammaglobulinemia makes it unlikely that the defect is due to a distinct gene rearrangement abnormality at a specific stage of B-cell maturation. Early recognition of B-cell deficiency and institution of adequate immunoglobulin replacement therapy can prevent extensive damage to the lungs and other life-threatening problems from infection and allow a relatively normal childhood and adult life.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Humoral immunodeficiency." Clin Immunol Immunopathol 40.1 (July 1986): 13-24. (Review)
PMID
2424651
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
40
Issue
1
Publish Date
1986
Start Page
13
End Page
24

Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children.

Children, aged 6 to 12 years, with fall-pollenosis symptoms, were evaluated for their response to a new antihistamine, terfenadine, in a multicenter (six centers) 1-week, double-blind, placebo-controlled trial. All had positive skin tests to grass/weed pollens and/or mold spores prevalent in the fall at each center. Patients were administered placebo or terfenadine as suspension on a randomized basis, with children weighing less than 30 kg receiving terfenadine suspension, 30 mg twice daily, and those weighing greater than 30 kg receiving 60 mg, twice daily. Of the 119 children enrolled, 79 received terfenadine and 40 received placebo. All but two (lost to follow-up) were included for the evaluation of drug safety, whereas 16 were excluded from the efficacy evaluation (11 receiving terfenadine and five receiving placebo) because of protocol noncompliance. Overall, varying degrees of control of symptoms were observed in 85% of the patients in the group taking terfenadine as compared to 60% in the group taking placebo. The symptoms of rhinorrhea, nasal congestion, and sneezing demonstrated the best response. There was no difference between the two groups in adverse events or side effects. Before and after treatment complete blood count, biochemical profile, and urinalysis revealed that there was no change from beginning to end and no difference between the groups. We conclude that terfenadine suspension is a safe, nonsedating antihistamine with an incidence of side effects no different from that of placebo. It is more effective than placebo in controlling symptoms of fall pollenosis in children.

Authors
Guill, MF; Buckley, RH; Rocha, W; Kemp, JP; Segal, AT; Shirley, LR; Tinkelman, DG; Shaath-Schwen, Z; Dietrich, KK; Wille, LJ
MLA Citation
Guill, MF, Buckley, RH, Rocha, W, Kemp, JP, Segal, AT, Shirley, LR, Tinkelman, DG, Shaath-Schwen, Z, Dietrich, KK, and Wille, LJ. "Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children." J Allergy Clin Immunol 78.1 Pt 1 (July 1986): 4-9.
PMID
2873161
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
78
Issue
1 Pt 1
Publish Date
1986
Start Page
4
End Page
9

MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF TERFENADINE SUSPENSION IN THE TREATMENT OF FALL-ALLERGIC RHINITIS IN CHILDREN

Authors
GUILL, MF; BUCKLEY, RH; ROCHA, W; KEMP, JP; SEGAL, AT; SHIRLEY, LR; TINKELMAN, DG; SHAATHSCHWEN, Z; DIETRICH, KK; WILLE, LJ; TSAI, TH
MLA Citation
GUILL, MF, BUCKLEY, RH, ROCHA, W, KEMP, JP, SEGAL, AT, SHIRLEY, LR, TINKELMAN, DG, SHAATHSCHWEN, Z, DIETRICH, KK, WILLE, LJ, and TSAI, TH. "MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF TERFENADINE SUSPENSION IN THE TREATMENT OF FALL-ALLERGIC RHINITIS IN CHILDREN." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 78.1 (July 1986): 4-9.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
78
Issue
1
Publish Date
1986
Start Page
4
End Page
9
DOI
10.1016/0091-6749(86)90107-7

SYMPOSIUM CHILDHOOD IMMUNODEFICIENCY DISORDERS - DIAGNOSIS, PREVENTION, AND MANAGEMENT - INTRODUCTION

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "SYMPOSIUM CHILDHOOD IMMUNODEFICIENCY DISORDERS - DIAGNOSIS, PREVENTION, AND MANAGEMENT - INTRODUCTION." CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY 40.1 (July 1986): 40-40.
Source
wos-lite
Published In
Clinical Immunology and Immunopathology
Volume
40
Issue
1
Publish Date
1986
Start Page
40
End Page
40

Variability of IgE protein measurement in cell-culture supernatants: results from a multicenter collaborative study.

The sensitivity, specificity, and precision of immunoassays for quantitation of IgE in cell-culture supernatants were tested in a multicenter trial involving 22 laboratories. Fourteen coded test samples included cell-culture medium alone, culture medium with varying concentrations of polyclonal or myeloma IgE, and medium from unstimulated or pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cell (PBMC)-culture supernatants. Two laboratories reported measurable IgE in non-IgE-containing control samples. Although the IgE content of a single 0.50 ng/ml polyclonal IgE sample should have been measured easily by the claims of all laboratories, only 13 laboratories measured IgE in this sample in 22 of the 48 assays. Most laboratories could measure both polyclonal and myeloma IgE at 5.0 ng/ml; however, the IgE determinations for the myeloma proteins were nearer the predicted value. Although 15 laboratories found measurable IgE in the PWM-stimulated PBMC-culture supernatants from a single nonatopic donor, the levels did not differ significantly from that measured in unstimulated PBMC-culture supernatants. Three laboratories reported considerably higher IgE levels in the PWM-stimulated PBMC-culture supernatants than in other PBMC-culture supernatants. Only 13 laboratories could quantitate IgE in each of coded duplicate samples containing 0.50 ng/ml polyclonal IgE. These findings indicate a wide variability in the sensitivity, specificity, and precision of assays used to quantitate low levels of IgE protein. Investigators should be encouraged to make greater use of existing national and international reference materials in the standardization and performance of their IgE immunoassays.

Authors
Helm, RM; Buckley, RH; Adkinson, NF; Squillace, DL; Gleich, GJ; Yunginger, JW
MLA Citation
Helm, RM, Buckley, RH, Adkinson, NF, Squillace, DL, Gleich, GJ, and Yunginger, JW. "Variability of IgE protein measurement in cell-culture supernatants: results from a multicenter collaborative study." J Allergy Clin Immunol 77.6 (June 1986): 880-890.
PMID
3711555
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
77
Issue
6
Publish Date
1986
Start Page
880
End Page
890

Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation.

Recent advances in the prevention of graft-vs-host disease (GVHD) have allowed the use of haploidentical bone marrow cells for correction of lethal genetic defects of the immune system. Sequential analyses of blood lymphocyte phenotypes and functions were done before and after transplantation of haploidentical marrow stem cells into 17 infants with severe primary T cell deficiencies. The marrow was depleted of post-thymic T cells and most other mature marrow cells by soy lectin agglutination and sheep erythrocyte rosetting. The studies were performed to define the time course and extent of appearance of immune function, and to identify factors leading to resistance to engraftment. No pretransplant immunosuppression was used. T cell function was detected between 34 and 287 days after transplantation, but a sharp rise usually occurred between 84 and 115 days, and normal function was reached between 113 and 210 days. Fifteen of the patients are alive from 6 to 41 mo post-transplantation, 12 have improved or have normal T lymphocyte function, and nine have proven T cell chimerism. Increased immunoglobulins of several isotypes have been noted in 11 patients and specific antibodies in seven patients, although B cell chimerism has been detected in only one patient. B cell function required 2 to 2.5 yr for normalization. No GVHD occurred in 14 patients, and the other three had only transient mild skin rashes. Two patients died of viral infections. Failure to engraft was correlated with some pre-transplant lymphocyte responses to mitogens and allogeneic cells (three cases), but not with the presence of pre-transplant natural killer cell function (five cases) nor with the presence of purine salvage pathway enzyme deficiencies (four cases). The latter, however, was associated with poor lymphoid function in two patients. These studies indicate that the thymic microenvironment of most infants with severe combined immunodeficiency disease is capable of differentiating donor stem cells to mature and functioning T lymphocytes which can cooperate with apparently normal host B cells for antibody production.

Authors
Buckley, RH; Schiff, SE; Sampson, HA; Schiff, RI; Markert, ML; Knutsen, AP; Hershfield, MS; Huang, AT; Mickey, GH; Ward, FE
MLA Citation
Buckley, RH, Schiff, SE, Sampson, HA, Schiff, RI, Markert, ML, Knutsen, AP, Hershfield, MS, Huang, AT, Mickey, GH, and Ward, FE. "Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation." J Immunol 136.7 (April 1, 1986): 2398-2407.
PMID
2869085
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
136
Issue
7
Publish Date
1986
Start Page
2398
End Page
2407

EXPRESSION OF GENE DEFECT IN X-LINKED AGAMMAGLOBULINEMIA (XLA) IS INTRINSIC TO THE B-CELL LINEAGE

Authors
CONLEY, ME; BUCKLEY, RH; RASKIND, WH; FIALKOW, PJ
MLA Citation
CONLEY, ME, BUCKLEY, RH, RASKIND, WH, and FIALKOW, PJ. "EXPRESSION OF GENE DEFECT IN X-LINKED AGAMMAGLOBULINEMIA (XLA) IS INTRINSIC TO THE B-CELL LINEAGE." CLINICAL RESEARCH 34.2 (April 1986): A668-A668.
Source
wos-lite
Published In
Clinical Research
Volume
34
Issue
2
Publish Date
1986
Start Page
A668
End Page
A668

EXPRESSION OF GENE DEFECT IN X-LINKED AGAMMAGLOBULINEMIA (XLA) IS INTRINSIC TO THE B-CELL LINEAGE

Authors
CONLEY, ME; BUCKLEY, RH; RASKIND, WH; FIALKOW, PJ
MLA Citation
CONLEY, ME, BUCKLEY, RH, RASKIND, WH, and FIALKOW, PJ. "EXPRESSION OF GENE DEFECT IN X-LINKED AGAMMAGLOBULINEMIA (XLA) IS INTRINSIC TO THE B-CELL LINEAGE." PEDIATRIC RESEARCH 20.4 (April 1986): A301-A301.
Source
wos-lite
Published In
Pediatric Research
Volume
20
Issue
4
Publish Date
1986
Start Page
A301
End Page
A301

THE USE OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) PREPARATIONS IN THE TREATMENT OF CHRONIC ENTEROVIRAL INFECTIONS

Authors
MCKINNEY, RE; MARKERT, ML; WILLIAMS, LW; BUCKLEY, RH; WILFERT, CM
MLA Citation
MCKINNEY, RE, MARKERT, ML, WILLIAMS, LW, BUCKLEY, RH, and WILFERT, CM. "THE USE OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) PREPARATIONS IN THE TREATMENT OF CHRONIC ENTEROVIRAL INFECTIONS." PEDIATRIC RESEARCH 20.4 (April 1986): A297-A297.
Source
wos-lite
Published In
Pediatric Research
Volume
20
Issue
4
Publish Date
1986
Start Page
A297
End Page
A297

RESPONSES TO RECIPIENT AND DONOR B-CELLS BY GENETICALLY DONOR T-CELLS FROM HUMAN HAPLOIDENTICAL CHIMERAS

Authors
SCHIFF, SE; SAMPSON, HA; BUCKLEY, RH
MLA Citation
SCHIFF, SE, SAMPSON, HA, and BUCKLEY, RH. "RESPONSES TO RECIPIENT AND DONOR B-CELLS BY GENETICALLY DONOR T-CELLS FROM HUMAN HAPLOIDENTICAL CHIMERAS." CLINICAL RESEARCH 34.2 (April 1986): A850-A850.
Source
wos-lite
Published In
Clinical Research
Volume
34
Issue
2
Publish Date
1986
Start Page
A850
End Page
A850

Development of IgA and IgG2 subclass deficiency after sulfasalazine therapy.

Authors
Leickly, FE; Buckley, RH
MLA Citation
Leickly, FE, and Buckley, RH. "Development of IgA and IgG2 subclass deficiency after sulfasalazine therapy." J Pediatr 108.3 (March 1986): 481-482.
PMID
2869115
Source
pubmed
Published In
The Journal of Pediatrics
Volume
108
Issue
3
Publish Date
1986
Start Page
481
End Page
482

Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA.

Authors
Burks, AW; Sampson, HA; Buckley, RH
MLA Citation
Burks, AW, Sampson, HA, and Buckley, RH. "Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA." N Engl J Med 314.9 (February 27, 1986): 560-564.
PMID
3945295
Source
pubmed
Published In
The New England journal of medicine
Volume
314
Issue
9
Publish Date
1986
Start Page
560
End Page
564
DOI
10.1056/NEJM198602273140907

Advances in the diagnosis and treatment of primary immunodeficiency diseases.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Advances in the diagnosis and treatment of primary immunodeficiency diseases." Arch Intern Med 146.2 (February 1986): 377-384.
PMID
3511876
Source
pubmed
Published In
Archives of internal medicine
Volume
146
Issue
2
Publish Date
1986
Start Page
377
End Page
384

ANAPHYLACTIC REACTIONS FOLLOWING GAMMA-GLOBULIN ADMINISTRATION IN PATIENTS WITH HYPOGAMMAGLOBULINEMIA - DETECTION OF IGE ANTIBODIES TO IGA

Authors
BURKS, AW; SAMPSON, HA; BUCKLEY, RH
MLA Citation
BURKS, AW, SAMPSON, HA, and BUCKLEY, RH. "ANAPHYLACTIC REACTIONS FOLLOWING GAMMA-GLOBULIN ADMINISTRATION IN PATIENTS WITH HYPOGAMMAGLOBULINEMIA - DETECTION OF IGE ANTIBODIES TO IGA." CLINICAL RESEARCH 34.1 (January 1986): A246-A246.
Source
wos-lite
Published In
Clinical Research
Volume
34
Issue
1
Publish Date
1986
Start Page
A246
End Page
A246

IMMUNODEFICIENCY WITH PURINE SALVAGE PATHWAY ENZYME DEFICIENCIES - EVALUATION OF THERAPIES

Authors
MARKERT, ML; HERSHFIELD, MS; SCHIFF, SE; SAMPSON, HA; SCHIFF, RI; BUCKLEY, RH
MLA Citation
MARKERT, ML, HERSHFIELD, MS, SCHIFF, SE, SAMPSON, HA, SCHIFF, RI, and BUCKLEY, RH. "IMMUNODEFICIENCY WITH PURINE SALVAGE PATHWAY ENZYME DEFICIENCIES - EVALUATION OF THERAPIES." January 1986.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
77
Issue
1
Publish Date
1986
Start Page
190
End Page
190

Introduction

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Introduction." Clinical Immunology and Immunopathology 40.1 (1986): 4--.
Source
scival
Published In
Clinical Immunology and Immunopathology
Volume
40
Issue
1
Publish Date
1986
Start Page
4-

Variability in B cell maturation and differentiation in X-linked agammaglobulinemia

Among seven males with X-linked agammaglobulinemia in an extended pedigree, serum immunoglobulins and antibodies were extremely low in all but one who had a normal IgA (78 mg/dl) and tetanus antibodies (1:19,683). Following bacteriophage Φ X 174 immunizations, the oldest failed to clear phage and had no primary or secondary antibody responses. The youngest had normal phage clearance, low primary and secondary antibody responses, and no amplification or switching to IgG. The other four affected had normal or slightly delayed phage clearance, low primary and seconary responses, but some amplification and switching from IgM to IgG which increased with age. Normal percentages of surface immunoglobulin positive cells were present in the two youngest patients, but all seven affected had very low percentages of cells reacting with monoclonal antibodies to B cell surface antigens. Immunoglobulin production by cultured blood B cells were very low and not increased by pokeweed mitogen. However, a majority of Epstein-Barr virus (EBV)-transformed lymphoblastoid cells derived from the blood of four of the patients bore IgD and IgM and reacted with all of the monoclonal antibodies to B cell antigens. Culture supernatants from those lines contained significant quantities of IgM and lesser amounts of IgG and IgA. The studies presented here provide further support for the hypothesis that the primary abnormality in X-linked agammaglobulinemia affects B cells at more than one stage of development rather than just at the level of the pre-B cell.

Authors
Leickley, FE; Buckley, R
MLA Citation
Leickley, FE, and Buckley, R. "Variability in B cell maturation and differentiation in X-linked agammaglobulinemia." Clinical and Experimental Immunology 65.1 (1986): 90-99.
PMID
3491702
Source
scival
Published In
Clinical and Experimental Immunology
Volume
65
Issue
1
Publish Date
1986
Start Page
90
End Page
99

Certification in diagnostic laboratory immunology

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Certification in diagnostic laboratory immunology." Annals of Internal Medicine 104.3 (1986): 435--.
Source
scival
Published In
Annals of Internal Medicine
Volume
104
Issue
3
Publish Date
1986
Start Page
435-

Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children

Children, aged 6 to 12 years, with fall-pollenosis symptoms, were evaluated for their response to a new antihistamine, terfenadine, in a multicenter (six centers) I-week, double-blind, placebo controlled trial. All had positive skin tests to grass/weed pollens and/or mold spores prevalent in the fall at each center. Patients were administered placebo or terfenadine as suspension on a randomized basis, with children weighing <30 kg receiving terfenadine suspension, 30 mg twice daily, and those weighing >30 kg receiving 60 mg, twice daily. Of the 119 children enrolled. 79 received terfenadine and 40 received placebo. All but two (lost to follow-up) were included for the evaluation of drug safety, whereas 16 were excluded from the efficacy evaluation (11 receiving terfenadine and five receiving placebo) because of protocol noncompliance. Overall, varying degrees of control of symptoms were observed in 85% of the patients in the group taking terfenadine as compared to 60% in the group taking placebo. The symptoms of rhinorrhea, nasal congestion, and sneezing demonstrated the best response. There was no difference between the two groups in adverse events or side effects. Before and after treatment complete blood count, biochemical profile, and urinalysis revealed that there was no change from beginning to end and no difference between the groups. We conclude that terfenadine suspension is a safe, nonsedating antihistamine with an incidence of side effects no different from that of placebo. It is more effective than placebo in controlling symptoms of fall pollenosis in children. © 1986.

Authors
Guill, MF; Buckley, RH; Jr, WR; Kemp, JP; Sega, AT; Shirley, LR; Tinkelman, DG; Shaath-Schwen, Z; Dietrich, KK; Wille, LJ; Tsai, TH
MLA Citation
Guill, MF, Buckley, RH, Jr, WR, Kemp, JP, Sega, AT, Shirley, LR, Tinkelman, DG, Shaath-Schwen, Z, Dietrich, KK, Wille, LJ, and Tsai, TH. "Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children." The Journal of Allergy and Clinical Immunology 78.1 PART 1 (1986): 4-9.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
78
Issue
1 PART 1
Publish Date
1986
Start Page
4
End Page
9

Appearance of multiple benign paraproteins during early engraftment of soy lectin T cell-depleted haploidentical bone marrow cells in severe combined immunodeficiency

Recent advances in the prevention of graft-versus-host disease through postthymic T-cell depletion have allowed the use of haploidentical bone marrow cells for immunologic reconstitution of severe combined immunodeficiency disease. We report a male infant with severe combined immunodeficiency (with normal adenosine deaminase) who developed two IgG kappa and one IgA lambda paraproteins 7 weeks following the administration of 1.4×109 maternal bone marrow cells depleted of postthymic T cells by soy lectin agglutination and sheep erythrocyte rosetting. Serum IgG rose from 128 to 820 mg/dl, and IgA from 0 to 2400 mg/dl, peaking at 10 weeks postgrafting. By 14 weeks posttransplantation T-cell numbers and function had risen to normal (all dividing T cells had the donor karyotype) and paraprotein concentrations began to decline. These observations strongly suggest that the later-appearing T cells regulated the B-cell clones from which the paraproteins were derived. Failure of such function to appear could account for the increased incidence of B-cell lymphomas in severe combined immunodeficiency. © 1986 Plenum Publishing Corporation.

Authors
Ghory, P; Schiff, S; Buckley, R
MLA Citation
Ghory, P, Schiff, S, and Buckley, R. "Appearance of multiple benign paraproteins during early engraftment of soy lectin T cell-depleted haploidentical bone marrow cells in severe combined immunodeficiency." Journal of Clinical Immunology 6.2 (1986): 161-169.
PMID
3519654
Source
scival
Published In
Journal of Clinical Immunology
Volume
6
Issue
2
Publish Date
1986
Start Page
161
End Page
169
DOI
10.1007/BF00918749

Workshop 7: Special pediatric problems

The assessment of NBAAD in pediatric patients is essential because asthma is common in children. Special problems of drug assessment in children should be considered in the context of various pediatric growth periods: (1) adolescence; (2) childhood (2 years to onset of adolescence); (3) infants/toddler (1 month to 2 years); and (4) neonatal (birth to 1 month). Rapid acceleration of growth and maturation are special problems in adolescence. In addition, awareness about safety, possible drug abuse, and compliance must be considered in this age group. Drug studies should also take into account the fact that natural remissions may occur more frequently in teenagers, especially in boys. In the childhood age group, asthma is more likely to be induced by respiratory viral infections; various endocrine parameters need to be followed more closely; and special attention should be paid to the detection of variations in growth and bone age. Dose ranging effects should be established in the very early stages of drug development and the kinetics of drug action should be followed in cases in which proper assays are available. Except in very young children, parameters for measuring drug effectiveness are the same as in adults. Special instructions should be devised for aerosolized medications if the drug is available only in this form. Ethical constraints in children are key problems. Double-blind testing with a placebo control is not advisable in the younger groups of children. Instead, drugs should be tested against other agents of known efficacy. Research in infants should be deferred until substantial evidence of safety and effectiveness has been gathered in older children or adults. The commercial marketing of drugs of potential use to children should be deferred until studies in older children and adolescents have been included in the FDA review process. © 1986.

Authors
Siegel, SC; Sogn, DD; Bierman, CW; Buckley, RH; Ellis, EF; Fischer, TJ; Levinson, H; Sly, RM; Westlin, WF
MLA Citation
Siegel, SC, Sogn, DD, Bierman, CW, Buckley, RH, Ellis, EF, Fischer, TJ, Levinson, H, Sly, RM, and Westlin, WF. "Workshop 7: Special pediatric problems." The Journal of Allergy and Clinical Immunology 78.3 PART 2 (1986): 534-540.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
78
Issue
3 PART 2
Publish Date
1986
Start Page
534
End Page
540

Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesion, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karyotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

Authors
DeVoe, PW; Buckley, RH; Reed Shirley, L; Darby, CP; Ward, FE; Mickey, GH; Raab-Traub, N; Vandenbark, GR
MLA Citation
DeVoe, PW, Buckley, RH, Reed Shirley, L, Darby, CP, Ward, FE, Mickey, GH, Raab-Traub, N, and Vandenbark, GR. "Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections." Clinical Immunology and Immunopathology 34.1 (January 1, 1985): 48-59.
Source
scopus
Published In
Clinical Immunology and Immunopathology
Volume
34
Issue
1
Publish Date
1985
Start Page
48
End Page
59
DOI
10.1016/0090-1229(85)90005-4

IgE Fc receptor positive T and B lymphocytes in patients with the hyper IgE syndrome.

The percentages of peripheral blood lymphocytes (PBL), bearing Fc receptors for IgE (Fc epsilon R) and IgG (Fc gamma R) were determined in four patients with the hyper IgE syndrome by a rosette assay employing IgE and IgG coated fixed ox erythrocytes. The patients had 8 +/- 3% Fc epsilon R+ and 13 +/- 8% Fc gamma R+ PBL, compared to 1.2 +/- 1% Fc epsilon R+ and 17 +/- 4% Fc gamma R+ PBL for control donors. T cells were isolated by rosetting with neuraminidase treated sheep erythrocytes (EN). Indirect immunofluorescence with Lyt 3 monoclonal antibody (MoAb) to the sheep erythrocyte receptor, followed by rosetting for Fc epsilon R and Fc gamma R showed that the patients' T cells contained less than 0.1% Fc epsilon R+ and 1.4 +/- 0.2% Fc gamma R+ cells; T cells from the control subjects contained less than 0.1% Fc epsilon R+ and 11 +/- 4% Fc gamma R+ cells. The non-T (EN rosette depleted) cells of the patients included 56 +/- 18% sIgM+/sIgD+, 45 +/- 9% Fc epsilon R+ and 35 +/- 27% Fc gamma R+ cells. Indirect immunofluorescence with MoAb to IgM, IgD, and NK cells (antibody B73.1) followed by rosetting for Fc epsilon R and Fc gamma R, indicated that 92 +/- 2% of the Fc epsilon R+ cells and 9 +/- 7% of the Fc gamma R+ cells were B cells (mu+/delta+), while 3 +/- 4% of the Fc epsilon R+ and 30 +/- 23% of the Fc gamma R+ cells were NK cells (B73.1+). Thus, most of the Fc epsilon R+ non-T cells were B cells, and only a small fraction appeared to be NK cells. On the other hand, Fc gamma R+ B cells were outnumbered by Fc gamma R+ NK cells (B73.1+) by three to one. The data indicate that patients with the hyper IgE syndrome have increased numbers of Fc gamma R+ PBL, most of them being B cells, whereas their T cells contain less than 0.1% Fc epsilon R+ cells.

Authors
Thompson, LF; Spiegelberg, HL; Buckley, RH
MLA Citation
Thompson, LF, Spiegelberg, HL, and Buckley, RH. "IgE Fc receptor positive T and B lymphocytes in patients with the hyper IgE syndrome." Clin Exp Immunol 59.1 (January 1985): 77-84.
PMID
3882288
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
59
Issue
1
Publish Date
1985
Start Page
77
End Page
84

Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections.

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

Authors
DeVoe, PW; Buckley, RH; Shirley, LR; Darby, CP; Ward, FE; Mickey, GH; Raab-Traub, N; Vandenbark, GR
MLA Citation
DeVoe, PW, Buckley, RH, Shirley, LR, Darby, CP, Ward, FE, Mickey, GH, Raab-Traub, N, and Vandenbark, GR. "Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections." Clin Immunol Immunopathol 34.1 (January 1985): 48-59.
PMID
2981167
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
34
Issue
1
Publish Date
1985
Start Page
48
End Page
59

IgE Fc receptor positive T, B and NK cells in patients with the hyper-IgE syndrome.

Patients with the hyper-IgE syndrome have greatly elevated percentages of IgE Fc receptor (Fc epsilon R)-positive B cells, but they have less than 0.1% Fc epsilon R+ T cells (T epsilon cells) and few, if any, Fc epsilon R+ natural killer cells. They also have markedly decreased numbers of IgG receptor positive (Fc gamma R+) T cells (T gamma cells). Patients with the hyper-IgE syndrome resemble in this respect patients with severe atopic dermatitis. Since a portion of T epsilon and T gamma cells of mildly atopic patients react with monoclonal antibody OKT8, they may have a suppressor function. However, whether the low number of T epsilon cells is responsible for the high IgE serum level in hyper-IgE syndrome and atopic dermatitis patients remains to be demonstrated. Attempts to obtain a reliable assay for human IgE synthesis in vitro to investigate the function of Fc epsilon R-positive lymphocytes proved to be difficult. Even isolated B cells from atopic donors seldom produced more than twice the quantity of IgE released from cells incubated in the presence of the protein synthesis inhibitor cycloheximide.

Authors
Spiegelberg, HL; Thompson, LF; McNeil, D; Buckley, RH
MLA Citation
Spiegelberg, HL, Thompson, LF, McNeil, D, and Buckley, RH. "IgE Fc receptor positive T, B and NK cells in patients with the hyper-IgE syndrome." Int Arch Allergy Appl Immunol 77.1-2 (1985): 277-279.
PMID
3159686
Source
pubmed
Published In
International Archives of Allergy and Applied Immunology
Volume
77
Issue
1-2
Publish Date
1985
Start Page
277
End Page
279

γ-Globulin replacement

Authors
Buckley, RH
MLA Citation
Buckley, RH. "γ-Globulin replacement." Clinics in Immunology and Allergy 5.1 (1985): 141-158.
Source
scival
Published In
Clinics in Immunology and Allergy
Volume
5
Issue
1
Publish Date
1985
Start Page
141
End Page
158

Development of immunity in severe primary T cell deficiency following haploidentical stem cell transplantation

Authors
Buckley, RH; Schiff, SE; Sampson, HA
MLA Citation
Buckley, RH, Schiff, SE, and Sampson, HA. "Development of immunity in severe primary T cell deficiency following haploidentical stem cell transplantation." Federation Proceedings 44.6 (1985): No.-8830.
Source
scival
Published In
Federation Proceedings
Volume
44
Issue
6
Publish Date
1985
Start Page
No.
End Page
8830

DEVELOPMENT OF IMMUNITY IN SEVERE PRIMARY T-CELL DEFICIENCY FOLLOWING HAPLOIDENTICAL STEM-CELL TRANSPLANTATION

Authors
BUCKLEY, RH; SCHIFF, SE; SAMPSON, HA; SCHIFF, RI; AMMERMAN, B; JOHNSON, RR; WARD, FE
MLA Citation
BUCKLEY, RH, SCHIFF, SE, SAMPSON, HA, SCHIFF, RI, AMMERMAN, B, JOHNSON, RR, and WARD, FE. "DEVELOPMENT OF IMMUNITY IN SEVERE PRIMARY T-CELL DEFICIENCY FOLLOWING HAPLOIDENTICAL STEM-CELL TRANSPLANTATION." FEDERATION PROCEEDINGS 44.6 (1985): 1922-1922.
Source
wos-lite
Published In
The FASEB Journal
Volume
44
Issue
6
Publish Date
1985
Start Page
1922
End Page
1922

GAMMA-GLOBULIN REPLACEMENT

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "GAMMA-GLOBULIN REPLACEMENT." CLINICS IN IMMUNOLOGY AND ALLERGY 5.1 (1985): 141-158.
Source
wos-lite
Published In
Immunology and Allergy Clinics of North America
Volume
5
Issue
1
Publish Date
1985
Start Page
141
End Page
158

SUCCESSFUL TREATMENT OF AUTOIMMUNE HEMOLYTIC-ANEMIA (AIHA) IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) WITH HIGH-DOSE INTRAVENOUS IMMUNE GLOBULIN (IVIG)

Authors
LEICKLY, FE; BUCKLEY, RH
MLA Citation
LEICKLY, FE, and BUCKLEY, RH. "SUCCESSFUL TREATMENT OF AUTOIMMUNE HEMOLYTIC-ANEMIA (AIHA) IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) WITH HIGH-DOSE INTRAVENOUS IMMUNE GLOBULIN (IVIG)." PEDIATRIC RESEARCH 19.4 (1985): A278-A278.
Source
wos-lite
Published In
Pediatric Research
Volume
19
Issue
4
Publish Date
1985
Start Page
A278
End Page
A278

DEVELOPMENT OF IMMUNITY IN SEVERE PRIMARY T-CELL DEFICIENCY FOLLOWING HAPLOIDENTICAL STEM-CELL TRANSPLANTATION

Authors
BUCKLEY, RH; SCHIFF, SE; SAMPSON, HA; SCHIFF, RI; AMMERMAN, BE; JOHNSON, RR; WARD, FE
MLA Citation
BUCKLEY, RH, SCHIFF, SE, SAMPSON, HA, SCHIFF, RI, AMMERMAN, BE, JOHNSON, RR, and WARD, FE. "DEVELOPMENT OF IMMUNITY IN SEVERE PRIMARY T-CELL DEFICIENCY FOLLOWING HAPLOIDENTICAL STEM-CELL TRANSPLANTATION." PEDIATRIC RESEARCH 19.4 (1985): A270-A270.
Source
wos-lite
Published In
Pediatric Research
Volume
19
Issue
4
Publish Date
1985
Start Page
A270
End Page
A270
DOI
10.1203/00006450-198504000-00990

Candida meningitis in two children with severe combined immunodeficiency.

Authors
Smego, RA; Devoe, PW; Sampson, HA; Perfect, JR; Wilfert, CM; Buckley, RH
MLA Citation
Smego, RA, Devoe, PW, Sampson, HA, Perfect, JR, Wilfert, CM, and Buckley, RH. "Candida meningitis in two children with severe combined immunodeficiency." J Pediatr 104.6 (June 1984): 902-904.
PMID
6726524
Source
pubmed
Published In
The Journal of Pediatrics
Volume
104
Issue
6
Publish Date
1984
Start Page
902
End Page
904

Severe combined immunodeficiency with natural killer-cell predominance: abrogation of graft-versus-host disease and immunologic reconstitution with HLA-identical bone marrow cells.

A 3 1/2-month-old infant with severe combined immunodeficiency was found to have an unusual blood lymphocyte phenotype. Thirty percent of her cells formed rosettes with sheep erythrocytes, but only 7.9% reacted with the pan T monoclonal antibody OKT3, and 5% reacted with an antibody (OKT4)-recognizing T-helper cells. Surprisingly 19.4% of her cells reacted with an antibody (OKT8)-recognizing T-suppressor cells and 94% reacted with OKT10 . Few reacted with other monoclonal antibodies detecting cellular activation antigens. Despite absence of T or B cell function, her monocyte-depleted blood lymphocytes caused a high degree of specific lysis of 51Cr-labeled K562 erythromyeloid cells in a natural killer-cell assay. Most of her lymphocytes were large and had azurophilic granules and a monocytoid nucleus. Because she had received a nonirradiated, unrelated red-cell transfusion 3 days earlier, 4.8 X 10(9) nucleated bone-marrow cells from her HLA-identical brother were given shortly after admission. Two days later a graft-versus-host reaction began but subsided completely within 3 days. On day 15 posttransplantation, a profuse secretory diarrhea began, accompanied by a rise in her serum IgE from 4 to 3000 IU. With engraftment, the number of T10+ cells and natural killer-cell function fell to normal, and full immunologic reconstitution was achieved.

Authors
Sindel, LJ; Buckley, RH; Schiff, SE; Ward, FE; Mickey, GH; Huang, AT; Naspitz, C; Koren, H
MLA Citation
Sindel, LJ, Buckley, RH, Schiff, SE, Ward, FE, Mickey, GH, Huang, AT, Naspitz, C, and Koren, H. "Severe combined immunodeficiency with natural killer-cell predominance: abrogation of graft-versus-host disease and immunologic reconstitution with HLA-identical bone marrow cells." J Allergy Clin Immunol 73.6 (June 1984): 829-836.
PMID
6233355
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
73
Issue
6
Publish Date
1984
Start Page
829
End Page
836

Use of a new chemically modified intravenous IgG preparation in severe primary humoral immunodeficiency: clinical efficacy and attempts to individualize dosage.

Sixteen patients with severe primary humoral immunodeficiency diseases were treated intravenously for 12 months with a beta-propiolactone stabilized preparation of IgG (Intraglobin) as part of a phase II study of safety and efficacy. In order to evaluate the metabolism of IgG in these patients and to determine whether increased doses of IgG would lead to a decrease in the rate of infections, the study was divided into two periods. All patients were infused with a standard dose of 100 mg/kg/month for 6 months and the peak and trough serum IgG concentrations were determined. The half-life of the IgG was determined in each patient after the fourth month and this value was used to calculate the dose necessary to raise the trough serum IgG concentration to a minimum of 200 mg/dl. The patients received this individualized dose in the final 6 months and the half-life determination was repeated at the conclusion of the study. Only 3 of 10 patients who received a higher dose in the second period had a substantial increase in trough serum IgG concentrations, but the failure to achieve higher concentrations was not due to a shortening of the half-life. The Intraglobin was well tolerated with no patient unable to complete the study due to side-effects. Ten percent of the infusions were associated with minor, self-limited reactions, with 16 of the 19 reactions occurring in the first 6 months. There were no life-threatening infections during the 12-month period. A total of 105 episodes of infections were recorded, but only a cumulative total of 51 days of normal school or work activity were lost by the 16 patients during the 12 months of the trial period. Most infectious episodes were due to chronic bronchitis, sinusitis, and otitis. There was no reduction in the number of infections in the second, higher dose period of the study; however, as there was little increase in serum IgG concentration, more data are required before it will be possible to determine if the incidence of chronic infections can be reduced by a further increase in the serum IgG concentration.

Authors
Schiff, RI; Rudd, C; Johnson, R; Buckley, RH
MLA Citation
Schiff, RI, Rudd, C, Johnson, R, and Buckley, RH. "Use of a new chemically modified intravenous IgG preparation in severe primary humoral immunodeficiency: clinical efficacy and attempts to individualize dosage." Clin Immunol Immunopathol 31.1 (April 1984): 13-23.
PMID
6421523
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
31
Issue
1
Publish Date
1984
Start Page
13
End Page
23

IgE Fc receptor positive lymphocytes in patients with the hyper-IgE syndrome

Authors
Spiegelberg, HL; Thompson, LF; Buckley, RH
MLA Citation
Spiegelberg, HL, Thompson, LF, and Buckley, RH. "IgE Fc receptor positive lymphocytes in patients with the hyper-IgE syndrome." Federation Proceedings 43.7 (1984): no.-3209.
Source
scival
Published In
Federation Proceedings
Volume
43
Issue
7
Publish Date
1984
Start Page
no.
End Page
3209

ANAPHYLACTIC REACTIONS IN COMMON VARIABLE AGAMMAGLOBULINEMIA (CVA-GAMMA) - TREATMENT WITH IGA-DEFICIENT INTRAVENOUS IMMUNE GLOBULIN (IVIG)

Authors
BURKS, AW; BUCKLEY, RH
MLA Citation
BURKS, AW, and BUCKLEY, RH. "ANAPHYLACTIC REACTIONS IN COMMON VARIABLE AGAMMAGLOBULINEMIA (CVA-GAMMA) - TREATMENT WITH IGA-DEFICIENT INTRAVENOUS IMMUNE GLOBULIN (IVIG)." CLINICAL RESEARCH 32.5 (1984): A891-A891.
Source
wos-lite
Published In
Clinical Research
Volume
32
Issue
5
Publish Date
1984
Start Page
A891
End Page
A891

In Reply

Authors
Buckley, RH
MLA Citation
Buckley, RH. "In Reply." JAMA: The Journal of the American Medical Association 250.22 (December 9, 1983): 3047-3048. (Letter)
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
22
Publish Date
1983
Start Page
3047
End Page
3048
DOI
10.1001/jama.1983.03340220019018

Atopic Dermatitis—A New Therapeutic Regimen-Reply

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Atopic Dermatitis—A New Therapeutic Regimen-Reply." JAMA: The Journal of the American Medical Association 250.21 (December 2, 1983): 2927-2927.
Source
crossref
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
21
Publish Date
1983
Start Page
2927
End Page
2927
DOI
10.1001/jama.1983.03340210024010

Immunodeficiency.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Immunodeficiency." J Allergy Clin Immunol 72.6 (December 1983): 627-641. (Review)
PMID
6417214
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
72
Issue
6
Publish Date
1983
Start Page
627
End Page
641

Food Allergy-Reply

Authors
Metcalfe, DD
MLA Citation
Metcalfe, DD. "Food Allergy-Reply." JAMA: The Journal of the American Medical Association 250.20 (November 25, 1983): 2792-2792.
Source
crossref
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
20
Publish Date
1983
Start Page
2792
End Page
2792
DOI
10.1001/jama.1983.03340200025018

Implications of "certification in diagnostic laboratory immunology" for the training and practice in allergy-immunology.

Authors
Kohler, PF; Buckley, RH; Bloch, KJ
MLA Citation
Kohler, PF, Buckley, RH, and Bloch, KJ. "Implications of "certification in diagnostic laboratory immunology" for the training and practice in allergy-immunology." J Allergy Clin Immunol 72.2 (August 1983): 121-122.
PMID
6886251
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
72
Issue
2
Publish Date
1983
Start Page
121
End Page
122

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.

Authors
Haynes, BF; Warren, RW; Buckley, RH; McClure, JE; Goldstein, AL; Henderson, FW; Hensley, LL; Eisenbarth, GS
MLA Citation
Haynes, BF, Warren, RW, Buckley, RH, McClure, JE, Goldstein, AL, Henderson, FW, Hensley, LL, and Eisenbarth, GS. "Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases." J Immunol 130.3 (March 1983): 1182-1188.
PMID
6600476
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
130
Issue
3
Publish Date
1983
Start Page
1182
End Page
1188

T cells and T-cell subsets in a large population of patients with primary immunodeficiency.

Authors
Buckley, RH; Gard, S; Schiff, RI; Sampson, HA
MLA Citation
Buckley, RH, Gard, S, Schiff, RI, and Sampson, HA. "T cells and T-cell subsets in a large population of patients with primary immunodeficiency." Birth Defects Orig Artic Ser 19.3 (1983): 187-191.
PMID
6228268
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
19
Issue
3
Publish Date
1983
Start Page
187
End Page
191

Individualization of gamma globulin dosage in patients with humoral immunodeficiency.

Authors
Schiff, RI; Rudd, C; Johnson, R; Buckley, RH
MLA Citation
Schiff, RI, Rudd, C, Johnson, R, and Buckley, RH. "Individualization of gamma globulin dosage in patients with humoral immunodeficiency." Birth Defects Orig Artic Ser 19.3 (1983): 209-212.
PMID
6197106
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
19
Issue
3
Publish Date
1983
Start Page
209
End Page
212

Severe combined immunodeficiency (SCID) with natural killer (NK) cell predominance.

Authors
Buckley, RH; Gard, S; Haynes, BF; Sindel, LJ; Davis, K; Sampson, HA; Ruff, ME; Koren, HS
MLA Citation
Buckley, RH, Gard, S, Haynes, BF, Sindel, LJ, Davis, K, Sampson, HA, Ruff, ME, and Koren, HS. "Severe combined immunodeficiency (SCID) with natural killer (NK) cell predominance." Birth Defects Orig Artic Ser 19.3 (1983): 101-104.
PMID
6360230
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
19
Issue
3
Publish Date
1983
Start Page
101
End Page
104

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Authors
Haynes, BF; Warren, RW; Buckley, RH; McClure, JE; Goldstein, AL; Henderson, FW; Hensley, LL; Eisenbarth, GS
MLA Citation
Haynes, BF, Warren, RW, Buckley, RH, McClure, JE, Goldstein, AL, Henderson, FW, Hensley, LL, and Eisenbarth, GS. "Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases." Birth Defects Orig Artic Ser 19.3 (1983): 255-258.
PMID
6606445
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
19
Issue
3
Publish Date
1983
Start Page
255
End Page
258

Atopic dermatitis - A new therapeutic regimen

Authors
Jr, SA; Buckley, RH
MLA Citation
Jr, SA, and Buckley, RH. "Atopic dermatitis - A new therapeutic regimen." Journal of the American Medical Association 250.21 (1983): 2926-2927.
PMID
6644970
Source
scival
Published In
Journal of the American Medical Association
Volume
250
Issue
21
Publish Date
1983
Start Page
2926
End Page
2927
DOI
10.1001/jama.250.21.2926

POSSIBLE IMMUNOGLOBULIN DEFICIENCY - REPLY

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "POSSIBLE IMMUNOGLOBULIN DEFICIENCY - REPLY." JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 250.22 (1983): 3047-3048.
Source
wos-lite
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
22
Publish Date
1983
Start Page
3047
End Page
3048

ATOPIC-DERMATITIS - A NEW THERAPEUTIC REGIMEN - REPLY

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "ATOPIC-DERMATITIS - A NEW THERAPEUTIC REGIMEN - REPLY." JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 250.21 (1983): 2927-2927.
Source
wos-lite
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
21
Publish Date
1983
Start Page
2927
End Page
2927

COMPARISON OF CORD AND ADULT T-CELL SUPPRESSOR FUNCTIONS IN 2 ASSAYS OF B-CELL DIFFERENTIATION

Authors
SINDEL, LJ; BUCKLEY, RH
MLA Citation
SINDEL, LJ, and BUCKLEY, RH. "COMPARISON OF CORD AND ADULT T-CELL SUPPRESSOR FUNCTIONS IN 2 ASSAYS OF B-CELL DIFFERENTIATION." FEDERATION PROCEEDINGS 42.4 (1983): 953-953.
Source
wos-lite
Published In
The FASEB Journal
Volume
42
Issue
4
Publish Date
1983
Start Page
953
End Page
953

ANTIBODY DEFICIENCY WITH NORMAL IMMUNE GLOBULINS - A DEFECT IN IMMUNE REGULATION

Authors
OCHS, HD; LINDGREN, CG; BUCKLEY, RH; WEDGWOOD, RJ
MLA Citation
OCHS, HD, LINDGREN, CG, BUCKLEY, RH, and WEDGWOOD, RJ. "ANTIBODY DEFICIENCY WITH NORMAL IMMUNE GLOBULINS - A DEFECT IN IMMUNE REGULATION." CLINICAL RESEARCH 31.1 (1983): A119-A119.
Source
wos-lite
Published In
Clinical Research
Volume
31
Issue
1
Publish Date
1983
Start Page
A119
End Page
A119

FOOD ALLERGY - REPLY

Authors
BUCKLEY, RH; METCALFE, DD
MLA Citation
BUCKLEY, RH, and METCALFE, DD. "FOOD ALLERGY - REPLY." JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 250.20 (1983): 2792-2792.
Source
wos-lite
Published In
JAMA : the journal of the American Medical Association
Volume
250
Issue
20
Publish Date
1983
Start Page
2792
End Page
2792

Food Allergy

Authors
Buckley, RH; Metcalfe, D
MLA Citation
Buckley, RH, and Metcalfe, D. "Food Allergy." JAMA: The Journal of the American Medical Association 248.20 (November 26, 1982): 2627-2631.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2627
End Page
2631
DOI
10.1001/jama.1982.03330200051013

Developmental Immunology and the Immunodeficiency Diseases

Authors
Cooper, MD; Buckley, RH
MLA Citation
Cooper, MD, and Buckley, RH. "Developmental Immunology and the Immunodeficiency Diseases." JAMA: The Journal of the American Medical Association 248.20 (November 26, 1982): 2658-2669.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2658
End Page
2669
DOI
10.1001/jama.1982.03330200082017

Common ‘Allergic’ Skin Diseases

Authors
Buckley, RH; Mathews, KP
MLA Citation
Buckley, RH, and Mathews, KP. "Common ‘Allergic’ Skin Diseases." JAMA: The Journal of the American Medical Association 248.20 (November 26, 1982): 2611-2622.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2611
End Page
2622
DOI
10.1001/jama.1982.03330200035011

Developmental immunology and the immunodeficiency diseases.

Authors
Cooper, MD; Buckley, RH
MLA Citation
Cooper, MD, and Buckley, RH. "Developmental immunology and the immunodeficiency diseases." JAMA 248.20 (November 26, 1982): 2658-2669.
PMID
7143628
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2658
End Page
2669

Food allergy.

Authors
Buckley, RH; Metcalfe, D
MLA Citation
Buckley, RH, and Metcalfe, D. "Food allergy." JAMA 248.20 (November 26, 1982): 2627-2631.
PMID
7143624
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2627
End Page
2631

Common "allergic' skin diseases.

Authors
Buckley, RH; Mathews, KP
MLA Citation
Buckley, RH, and Mathews, KP. "Common "allergic' skin diseases." JAMA 248.20 (November 26, 1982): 2611-2622.
PMID
7143623
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
248
Issue
20
Publish Date
1982
Start Page
2611
End Page
2622

Abnormalities in the regulation of human IgE synthesis.

Authors
Buckley, RH; Sampson, HA; Fisher, PM; Becker, WG; Shirley, LR
MLA Citation
Buckley, RH, Sampson, HA, Fisher, PM, Becker, WG, and Shirley, LR. "Abnormalities in the regulation of human IgE synthesis." Ann Allergy 49.2 (August 1982): 67-72.
PMID
6980609
Source
pubmed
Published In
Annals of Allergy
Volume
49
Issue
2
Publish Date
1982
Start Page
67
End Page
72

Symptomatic giardiasis in three patients with X-linked agammaglobulinemia.

Authors
LoGalbo, PR; Sampson, HA; Buckley, RH
MLA Citation
LoGalbo, PR, Sampson, HA, and Buckley, RH. "Symptomatic giardiasis in three patients with X-linked agammaglobulinemia." J Pediatr 101.1 (July 1982): 78-80.
PMID
7201017
Source
pubmed
Published In
The Journal of Pediatrics
Volume
101
Issue
1
Publish Date
1982
Start Page
78
End Page
80

Monoclonal immunoglobulin-secreting lymphoma in a patient with severe combined immunodeficiency disease.

A 3.5 year old boy with X-linked severe combined immunodeficiency disease (SCID), who had been in laminar flow isolation throughout his life, developed a B cell tumour producing up to 3008 mg/dl of an IgM kappa paraprotein 1 month after infusion of both liver and thymus cells from a fetal donor and 6 months after the last of six fetal liver cell infusions given over a 3 year period. Pretransplant studies revealed a high percentage of circulating B lymphocytes. HLA typing suggests that the tumour was of host origin.

Authors
Shirley, LR; Buckley, RH; Borowitz, MJ; Welt, SI; Kostyu, DD
MLA Citation
Shirley, LR, Buckley, RH, Borowitz, MJ, Welt, SI, and Kostyu, DD. "Monoclonal immunoglobulin-secreting lymphoma in a patient with severe combined immunodeficiency disease." Clin Exp Immunol 48.3 (June 1982): 666-674.
PMID
6811170
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
48
Issue
3
Publish Date
1982
Start Page
666
End Page
674

Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: inadequacy of current dosage practices and approaches to the problem.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: inadequacy of current dosage practices and approaches to the problem." J Clin Immunol 2.2 Suppl (April 1982): 15S-21S.
PMID
6806314
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
2
Issue
2 Suppl
Publish Date
1982
Start Page
15S
End Page
21S

Use of intravenous gamma-globulin in antibody immunodeficiency: results of a multicenter controlled trial.

Authors
Ammann, AJ; Ashman, RF; Buckley, RH; Hardie, WR; Krantmann, HJ; Nelson, J; Ochs, H; Stiehm, ER; Tiller, T; Wara, DW; Wedgwood, R
MLA Citation
Ammann, AJ, Ashman, RF, Buckley, RH, Hardie, WR, Krantmann, HJ, Nelson, J, Ochs, H, Stiehm, ER, Tiller, T, Wara, DW, and Wedgwood, R. "Use of intravenous gamma-globulin in antibody immunodeficiency: results of a multicenter controlled trial." Clin Immunol Immunopathol 22.1 (January 1982): 60-67.
PMID
6749355
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
22
Issue
1
Publish Date
1982
Start Page
60
End Page
67

Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: inadequacy of current dosage practices and approaches to the problem

Thirty patients with well-defined primary immunodeficiency diseases seen at Duke University Medical Center between April of 1975 and November of 1981 were given modified immune serum globulin suitable for intravenous use (IGIV) for replacement therapy. Seven patients had infantile x-linked agammaglobulinemia (XAγ), three had x-linked immunodeficiency with hyper IgM (HypM), three had Wiskott-Aldrich syndrome, and 17 had common variable agammaglobulinemia (CVAγ). Twenty-two of the patients received a reduced and alkylated preparation (Gamimune®) over periods of up to five years and 21 have received a beta propriolactone-treated preparation (Intraglobulin®) over a period ranging to 7 months. Fourteen of the Gamimune-treated patients participated in the two-year crossover Phase II efficacy and safety study beginning in April of 1975 and 9 of these participated in the 6-month double-blind crossover study of 10% IGIV in glycine vs 5% IGIV in 10% maltose (Gamimune). Ten of the patients received Gamimune on a monthly basis for more than 5 years, with the other 12 receiving it for lesser periods of time. All patients received an initial loading dose of 200 mg/kg IgG and were maintained on 100 mg/kg/month thereafter. Adverse effects were most frequent with 10% IGIV in glycine and included primarily back and muscle pain, chills, nausea and vomiting; these have been rare with 5% IGIV in 10% maltose (Gamimune). No anaphylactic-type reactions occurred. No patient experienced adverse effects sufficiently severe to necessitate discontinuing a given infusion, and no patient dropped out of the study because of adverse effects. Patients participating in the two-year crossover study were given a choice as to the form of replacement therapy at the conclusion of the study: 10 elected to remain on Gamimune and the other four resumed plasma therapy; no patient elected to resume intramuscular ISG injections. Both intravenous preparations had excellent patient acceptability and have resulted in efficacy at least comparable to that of intramuscular ISG and plasma therapy. Patients with the Wiskott-Aldrich syndrome tolerated IGIV with no adverse effects and were cognizant of a reduction in their frequencies of pyogenic infections. A patient with persistent Echovirus meningoencephalitis was given 500 mg IgG/kg/month for 9 months but remained Echovirus positive.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: inadequacy of current dosage practices and approaches to the problem." Journal of Clinical Immunology 2.2 Suppl. (1982): 15S-21S.
Source
scival
Published In
Journal of Clinical Immunology
Volume
2
Issue
2 Suppl.
Publish Date
1982
Start Page
15S
End Page
21S

Effects of hydrocortisone (HC) on IgE synthesis by cultured human mononuclear cells (MNC)

Authors
Shirley, LR; Sampson, HA; Buckley, RH
MLA Citation
Shirley, LR, Sampson, HA, and Buckley, RH. "Effects of hydrocortisone (HC) on IgE synthesis by cultured human mononuclear cells (MNC)." Journal of Allergy and Clinical Immunology 69.1 II (1982): 258--.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
69
Issue
1 II
Publish Date
1982
Start Page
258-

COMPLEX GANGLIOSIDES AS MARKERS OF THYMIC EPITHELIUM - DEMONSTRATION OF DEFECTS IN THYMIC EPITHELIUM STRUCTURE AND GANGLIOSIDE EXPRESSION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE

Authors
HAYNES, BF; WARREN, RW; BUCKLEY, RH; MCCLURE, JE; GOLDSTEIN, AL; EISENBARTH, GS
MLA Citation
HAYNES, BF, WARREN, RW, BUCKLEY, RH, MCCLURE, JE, GOLDSTEIN, AL, and EISENBARTH, GS. "COMPLEX GANGLIOSIDES AS MARKERS OF THYMIC EPITHELIUM - DEMONSTRATION OF DEFECTS IN THYMIC EPITHELIUM STRUCTURE AND GANGLIOSIDE EXPRESSION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE." CLINICAL RESEARCH 30.2 (1982): A350-A350.
Source
wos-lite
Published In
Clinical Research
Volume
30
Issue
2
Publish Date
1982
Start Page
A350
End Page
A350

HUMAN CORD BLOOD (CB) LYMPHOCYTE-T HELPER AND SUPPRESSOR PHENOTYPES, IMMUNOGLOBULIN (IG) PRODUCTION, AND EFFECTS ON NORMAL ADULT IG PRODUCTION

Authors
LOGALBO, PR; BUCKLEY, RH
MLA Citation
LOGALBO, PR, and BUCKLEY, RH. "HUMAN CORD BLOOD (CB) LYMPHOCYTE-T HELPER AND SUPPRESSOR PHENOTYPES, IMMUNOGLOBULIN (IG) PRODUCTION, AND EFFECTS ON NORMAL ADULT IG PRODUCTION." FEDERATION PROCEEDINGS 41.3 (1982): 799-799.
Source
wos-lite
Published In
The FASEB Journal
Volume
41
Issue
3
Publish Date
1982
Start Page
799
End Page
799

LONG-TERM USE OF INTRAVENOUS IMMUNE GLOBULIN IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES - INADEQUACY OF CURRENT DOSAGE PRACTICES AND APPROACHES TO THE PROBLEM

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "LONG-TERM USE OF INTRAVENOUS IMMUNE GLOBULIN IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES - INADEQUACY OF CURRENT DOSAGE PRACTICES AND APPROACHES TO THE PROBLEM." JOURNAL OF CLINICAL IMMUNOLOGY 2.2 (1982): S15-S21.
Source
wos-lite
Published In
Journal of Clinical Immunology
Volume
2
Issue
2
Publish Date
1982
Start Page
S15
End Page
S21
DOI
10.1007/BF00918362

Elevated IgA concentration in milk produced by mothers delivered of preterm infants.

Concentrations of immunoglobulins G, M, and A were measured by double-antibody radioimmunoassay in morning milk samples collected during the first month postpartum from 35 mothers delivered of preterm infants and 14 mothers delivered of term infants. Mean concentrations of IgG (1.8, to 2.8 mg/gm protein) and IgM (2.8 to 11.7 mg/gm protein) were similar in milk from both groups of mothers. In contrast, IgA was present in significantly higher concentrations throughout the first month postpartum in milk from mothers delivered of preterm infants than in milk from those giving birth at term (P less than 0.01). To determine the effect of milk flow on IgA concentration, IgA was also measured in complete 24-hour milk collections; milk from mothers with preterm deliveries again contained significantly higher concentrations of IgA than milk from mothers with term deliveries (P less than 0.01). This higher IgA concentration was not secondary to method of milk expression. The concentration of IgA was found, however, to vary inversely with milk volume (P less than 0.01). Although mean values of milk volumes for the groups were not statistically different, the overall lower volumes of milk produced by mothers giving birth preterm resulted in comparable total IgA production per 24 hours. There were no differences in serum IgA concentrations of preterm infants fed their own mother's milk and comparable infants fed a cow milk formula, suggesting that IgA in milk is not absorbed from the intestine in significant amounts.

Authors
Gross, SJ; Buckley, RH; Wakil, SS; McAllister, DC; David, RJ; Faix, RG
MLA Citation
Gross, SJ, Buckley, RH, Wakil, SS, McAllister, DC, David, RJ, and Faix, RG. "Elevated IgA concentration in milk produced by mothers delivered of preterm infants." J Pediatr 99.3 (September 1981): 389-393.
PMID
7264792
Source
pubmed
Published In
The Journal of Pediatrics
Volume
99
Issue
3
Publish Date
1981
Start Page
389
End Page
393

Human IgE synthesis in vitro: a reassessment.

Authors
Sampson, HA; Buckley, RH
MLA Citation
Sampson, HA, and Buckley, RH. "Human IgE synthesis in vitro: a reassessment." J Immunol 127.3 (September 1981): 829-834.
PMID
7264304
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
127
Issue
3
Publish Date
1981
Start Page
829
End Page
834

Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi.

Among 245 cases of chronic granulomatous disease which were evaluated, fungal infection occurred in 20.4 percent. Fungi encountered include Aspergillus, Torulopsis and Candida. In 18 percent of the patients with fungal infection, the disease was limited to soft tissue or bone; all did well. Most of the patients had fungal pneumonia and/or widely disseminated disease; diagnosis was usually confirmed by open lung biopsy. Patients with pneumonia or disseminated disease who received no therapy succumbed to infection, whereas more than half the patients who received antifungal therapy were cured. Modalities of treatment included antifungal chemotherapy, surgical removal of infected tissue and granulocyte transfusion. Although several patients showed dramatic improvement during granulocyte transfusions given in combination with antifungal chemotherapy, the improvement achieved was not statistically significant when compared with that achieved with chemotherapy alone. These results emphasized the importance of phagocytic cells in defense against fungi and the need for further evaluation of granulocyte transfusion therapy in compromised hosts in whom fungal infections develop.

Authors
Cohen, MS; Isturiz, RE; Malech, HL; Root, RK; Wilfert, CM; Gutman, L; Buckley, RH
MLA Citation
Cohen, MS, Isturiz, RE, Malech, HL, Root, RK, Wilfert, CM, Gutman, L, and Buckley, RH. "Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi." Am J Med 71.1 (July 1981): 59-66.
PMID
7195647
Source
pubmed
Published In
The American Journal of Medicine
Volume
71
Issue
1
Publish Date
1981
Start Page
59
End Page
66

Regulation of IgE synthesis: introduction.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Regulation of IgE synthesis: introduction." Fed Proc 40.8 (June 1981): 2159-2161.
PMID
6453728
Source
pubmed
Published In
The FASEB Journal
Volume
40
Issue
8
Publish Date
1981
Start Page
2159
End Page
2161

In vitro studies of IgE synthesis by human blood mononuclear cells.

IgE was detected in increasing quantities in supernatants of cultured human blood mononuclear cells, with peak amounts being found in 7 to 12-day cultures. Inhibitors of protein synthesis or of cell division reduced IgE production. Significantly greater amounts of IgE were made by cells from patients with elevated serum IgE than by those from normal adults. Pokeweed mitogen caused modest (threefold) augmentation of IgE synthesis is normal control cultures but inhibited it in cultures from patients with elevated serum IgE. Co-culturing unfractionated mononuclear cells from some atopic patients with cells from normal people resulted in significant suppression of the expected amount of IgE synthesis but not of IgM or IgG production. This suggests that a suppressor cell population or function is present in normal adults that regulates B cell IgE synthesis and that patients with elevated IgE may be deficient in this function. Results of coculture studies with isolated T and B cell-enriched subpopulations support the possibility that such activity exists in normal T cell populations. The marked augmentation of IgE synthesis by patients' B cells when separated from their own T cells indicates that patients' T cells have some regulatory capacity, but control T cells were more potent in this regard.

Authors
Buckley, RH; Fiser, PM; Becker, WG
MLA Citation
Buckley, RH, Fiser, PM, and Becker, WG. "In vitro studies of IgE synthesis by human blood mononuclear cells." Fed Proc 40.8 (June 1981): 2167-2170.
PMID
7238900
Source
pubmed
Published In
The FASEB Journal
Volume
40
Issue
8
Publish Date
1981
Start Page
2167
End Page
2170

Colonic nodular lymphoid hyperplasia in a child with antibody deficiency and near-normal immunoglobulins.

Authors
Knutsen, AP; Merten, DF; Buckley, RH
MLA Citation
Knutsen, AP, Merten, DF, and Buckley, RH. "Colonic nodular lymphoid hyperplasia in a child with antibody deficiency and near-normal immunoglobulins." J Pediatr 98.3 (March 1981): 420-423.
PMID
7205452
Source
pubmed
Published In
The Journal of Pediatrics
Volume
98
Issue
3
Publish Date
1981
Start Page
420
End Page
423

Immunologic studies before and after splenectomy in a patient with the Wiskott-Aldrich syndrome.

Sequential studies of cellular and humoral immunity were conducted in an infant with the Wiskott-Aldrich syndrome prior to and after a splenectomy for uncontrollable hemorrhage. All measures of cellular immunity showed gradual improvement during the 8-month period after surgery. Serum isohemagglutinins, diphtheria and tetanus antibodies, and the percentage of immunoglobulin-bearing B cells did not change significantly from presplenectomy values. The serum IgE concentration declined from a high of 10,800 IU/ml at 1 month postsplenectomy to a low of 860 IU/ml at 5 months after surgery and the IgG concentration gradually decreased from a high of 1880 mg/dl presplenectomy to a low of 620 mg/dl 8 months later. The platelet count ranged from 64,000 to 206,000/mm3 for the first 6 months after splenectomy. It decreased precipitously 6.5 months after the operation; at the same time there was a marked rise in platelet-bound IgG antibody (PB-IgG). The PB-IgG declined rapidly following vincristine therapy and, after another rise, declined more gradually following steroid therapy.

Authors
Knutsen, AP; Rosse, WF; Kinney, TR; Buckley, RH
MLA Citation
Knutsen, AP, Rosse, WF, Kinney, TR, and Buckley, RH. "Immunologic studies before and after splenectomy in a patient with the Wiskott-Aldrich syndrome." J Clin Immunol 1.1 (January 1981): 13-19.
PMID
7334067
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
1
Issue
1
Publish Date
1981
Start Page
13
End Page
19

Effects of hydrocortisone and theophylline on mononuclear cell supernatant IgE concentrations

Authors
Shirley, LR; Buckley, RH
MLA Citation
Shirley, LR, and Buckley, RH. "Effects of hydrocortisone and theophylline on mononuclear cell supernatant IgE concentrations." Pediatric Research 15.4 II (1981): 967--.
Source
scival
Published In
Pediatric Research
Volume
15
Issue
4 II
Publish Date
1981
Start Page
967-

EFFECTS OF HYDROCORTISONE AND THEOPHYLLINE ON MONONUCLEAR CELL SUPERNATANT IGE CONCENTRATIONS

Authors
SHIRLEY, LR; BUCKLEY, RH
MLA Citation
SHIRLEY, LR, and BUCKLEY, RH. "EFFECTS OF HYDROCORTISONE AND THEOPHYLLINE ON MONONUCLEAR CELL SUPERNATANT IGE CONCENTRATIONS." PEDIATRIC RESEARCH 15.4 (1981): 603-603.
Source
wos-lite
Published In
Pediatric Research
Volume
15
Issue
4
Publish Date
1981
Start Page
603
End Page
603
DOI
10.1203/00006450-198104001-00992

INTRAVENOUS IMMUNE GLOBULIN IN 10-PERCENT MALTOSE - EVALUATION OF SAFETY AND PATIENT ACCEPTANCE

Authors
OCHS, HD; BUCKLEY, RH; PIROFSKY, B; FISCHER, SH; ROUSELL, RH; ANDERSON, CJ; WEDGWOOD, RJ
MLA Citation
OCHS, HD, BUCKLEY, RH, PIROFSKY, B, FISCHER, SH, ROUSELL, RH, ANDERSON, CJ, and WEDGWOOD, RJ. "INTRAVENOUS IMMUNE GLOBULIN IN 10-PERCENT MALTOSE - EVALUATION OF SAFETY AND PATIENT ACCEPTANCE." CLINICAL RESEARCH 29.1 (1981): A90-A90.
Source
wos-lite
Published In
Clinical Research
Volume
29
Issue
1
Publish Date
1981
Start Page
A90
End Page
A90

Presidential address. Reflections on the 1970s and a look to the future.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Presidential address. Reflections on the 1970s and a look to the future." J Allergy Clin Immunol 66.6 (December 1980): 432-437.
PMID
7000871
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
66
Issue
6
Publish Date
1980
Start Page
432
End Page
437

Safety and patient acceptability of intravenous immune globulin in 10% maltose.

The safety and patient acceptance of two preparations of modified (reduced and alkylated) immune globulin for intravenous use were evaluated; one preparation was formulated as a 5% solution in 10% maltose (IGIV-maltose), the other did not contain maltose (IGIV). In this double-blind trial each of 29 immunodeficient patients received three consecutive monthly infusions (100 or 150 mg/kg immune globulin) of one preparation before being crossed over to the other. Only 3 of 29 patients had adverse reactions when on IGIV-maltose, compared with 22 who had side-effects during infusions of IGIV (p < 0.001). Adverse reactions were recorded during 3 of 87 IGIV-maltose infusions and during 51 infusions with the maltose-free IGIV (p < 0.001). 27 patients expressed preference for IGIV-maltose. IGIV-maltose seems safe and will permit rapid infusion of large doses of immune globulin, thus improving the management of patients with antibody deficiency diseases.

Authors
Ochs, HD; Buckley, RH; Pirofsky, B; Fischer, SH; Rousell, RH; Anderson, CJ; Wedgwood, RJ
MLA Citation
Ochs, HD, Buckley, RH, Pirofsky, B, Fischer, SH, Rousell, RH, Anderson, CJ, and Wedgwood, RJ. "Safety and patient acceptability of intravenous immune globulin in 10% maltose." Lancet 2.8205 (November 29, 1980): 1158-1159.
PMID
6107768
Source
pubmed
Published In
The Lancet
Volume
2
Issue
8205
Publish Date
1980
Start Page
1158
End Page
1159

Medusa cells: the morphology and cytochemistry of common amoeboid variants of eosinophils.

Authors
Hanker, JS; Chandross, RJ; Weatherly, NF; Laszlo, J; Moore, JO; Buckley, RH; Ottolenghi, A
MLA Citation
Hanker, JS, Chandross, RJ, Weatherly, NF, Laszlo, J, Moore, JO, Buckley, RH, and Ottolenghi, A. "Medusa cells: the morphology and cytochemistry of common amoeboid variants of eosinophils." Histochem J 12.6 (November 1980): 701-715.
PMID
6449493
Source
pubmed
Published In
The Histochemical journal
Volume
12
Issue
6
Publish Date
1980
Start Page
701
End Page
715

IgA in saliva of breast-fed and bottle-fed infants.

Authors
Gross, SJ; Buckley, RH
MLA Citation
Gross, SJ, and Buckley, RH. "IgA in saliva of breast-fed and bottle-fed infants." Lancet 2.8193 (September 6, 1980): 543-. (Letter)
PMID
6105597
Source
pubmed
Published In
The Lancet
Volume
2
Issue
8193
Publish Date
1980
Start Page
543

Phenytoin hypersensitivity.

Authors
Josephs, SH; Rothman, SJ; Buckley, RH
MLA Citation
Josephs, SH, Rothman, SJ, and Buckley, RH. "Phenytoin hypersensitivity." J Allergy Clin Immunol 66.2 (August 1980): 166-172.
PMID
7400479
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
66
Issue
2
Publish Date
1980
Start Page
166
End Page
172

Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE.

Earlier studies of serum immunoglobulin D concentrations were hampered by the insensitivity of single radial diffusion, since most normal individuals have IgD concentrations in a range below or near the limit of sensitivity of that method. Using a sensitive double-antibody radioimmunoassay, we measured serum IgD in normal individuals from 28 weeks' gestational age to 70 years of age and in several groups of diseased individuals, many of whom had elevated serum IgE concentrations. The group mean serum IgD concentration in children one to 20 years of age was 13.65 IU/ml. Premature and term neonates had levels that did not differ significantly from each other (0.22 and 0.14 IU/ml, respectively), but that were far lower than serum IgD concentrations in normal children one to 20 years of age (P = less than 10-9), indicating that mature levels of IgD are achieved sometime during the first year of life. Normal adults aged 21 to 70 years, atopic children with or without eczema, children with serum IgE values greater than 2,000 IU/ml, and children with cystic fibrosis all had group mean IgD concentrations that did not differ significantly from that of normal children. In contrast, 20 patients with the hyper IgE syndrome had a mean serum IgD concentration of 94.22 IU/ml, significantly higher than the normal or any other group mean (P = less than 10-5).

Authors
Josephs, SH; Buckley, RH
MLA Citation
Josephs, SH, and Buckley, RH. "Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE." J Pediatr 96.3 Pt 1 (March 1980): 417-420.
PMID
7359233
Source
pubmed
Published In
The Journal of Pediatrics
Volume
96
Issue
3 Pt 1
Publish Date
1980
Start Page
417
End Page
420

IgA IN SALIVA OF BREAST-FED AND BOTTLE-FED INFANTS

Authors
Gross, SJ; Buckley, RH
MLA Citation
Gross, SJ, and Buckley, RH. "IgA IN SALIVA OF BREAST-FED AND BOTTLE-FED INFANTS." The Lancet 316.8193 (January 1, 1980): 543-. (Letter)
Source
scopus
Published In
The Lancet
Volume
316
Issue
8193
Publish Date
1980
Start Page
543
DOI
10.1016/S0140-6736(80)91876-0

Reflections on the 1970s and a look to the future

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Reflections on the 1970s and a look to the future." The Journal of Allergy and Clinical Immunology 66.6 (1980): 432-437.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
66
Issue
6
Publish Date
1980
Start Page
432
End Page
437

Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE

Earlier studies of serum immunoglobulin D concentrations were hampered by the insensitivity of single radial diffusion, since most normal individuals have IgD concentrations in a range below or near the limit of sensitivity of that method. Using a sensitive double-antibody radioimmunoassay, we measured serum IgD in normal individuals from 28 weeks' gestational age to 70 years of age and in several groups of diseased individuals, many of whom had elevated serum IgE concentrations. The group mean serum IgD concentration in children one to 20 years of age was 13.65 IU/ml. Premature and term neonates had levels that did not differ significantly from each other (0.22 and 0.14 IU/ml, respectively), but that were far lower than serum IgD concentrations in normal children one to 20 years of age (P=<10-9), indicating that mature levels of IgD are achieved sometime during the first year of life. Normal adults aged 21 to 70 years, atopic children with or without eczema, children with serum IgE values greater than 2,000 IU/ml, and children with cystic fibrosis all had group mean IgD concentrations that did not differ significantly from that of normal children. In contrast, 20 patients with the hyper IgE syndrome had a mean serum IgD concentration of 94.22 IU/ml, significantly higher than the normal or any other group mean (P=<10-5). © 1980 The C. V. Mosby Company.

Authors
Josephs, SH; Buckley, RH
MLA Citation
Josephs, SH, and Buckley, RH. "Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE." The Journal of Pediatrics 96.3 PART 1 (1980): 417-420.
Source
scival
Published In
The Journal of Pediatrics
Volume
96
Issue
3 PART 1
Publish Date
1980
Start Page
417
End Page
420

SERUM IGD CONCENTRATIONS IN NORMAL INFANTS, CHILDREN, AND ADULTS AND IN PATIENTS WITH ELEVATED IGE

Authors
JOSEPHS, SH; BUCKLEY, RH
MLA Citation
JOSEPHS, SH, and BUCKLEY, RH. "SERUM IGD CONCENTRATIONS IN NORMAL INFANTS, CHILDREN, AND ADULTS AND IN PATIENTS WITH ELEVATED IGE." JOURNAL OF PEDIATRICS 96.3 (1980): 417-420.
Source
wos-lite
Published In
The Journal of Pediatrics
Volume
96
Issue
3
Publish Date
1980
Start Page
417
End Page
420
DOI
10.1016/S0022-3476(80)80684-6

REGULATION OF IGE SYNTHESIS INVITRO - EFFECTS OF MITOGENS AND IRRADIATION OF T-CELLS

Authors
SAMPSON, HA; BUCKLEY, RH
MLA Citation
SAMPSON, HA, and BUCKLEY, RH. "REGULATION OF IGE SYNTHESIS INVITRO - EFFECTS OF MITOGENS AND IRRADIATION OF T-CELLS." FEDERATION PROCEEDINGS 39.3 (1980): 567-567.
Source
wos-lite
Published In
The FASEB Journal
Volume
39
Issue
3
Publish Date
1980
Start Page
567
End Page
567

Human IgE biosynthesis in vitro: studies with atopic and normal blood mononuclear cells and subpopulations.

Authors
Fiser, PM; Buckley, RH
MLA Citation
Fiser, PM, and Buckley, RH. "Human IgE biosynthesis in vitro: studies with atopic and normal blood mononuclear cells and subpopulations." J Immunol 123.4 (October 1979): 1788-1794.
PMID
314473
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
123
Issue
4
Publish Date
1979
Start Page
1788
End Page
1794

Hyperimmunoglobulinemia E syndrome: radiographic observations.

Susceptibility to recurrent staphylococcal cutaneous and respiratory infections beginning in infancy associated with extreme hyperimmunoglobulinemia E is a recently described primary immunodeficiency syndrome. Other clinical features include depressed cellular immunity and deficient antibody formation. Recurrent pneumonia and cyst formation with variable persistence and expansion characterized the radiographic couse in 11 patients. Five cysts resolved with continuous antistaphylococcal therapy; 2 were resected without recurrence; and 4 persisted after surgery and/or antibiotics (2--8 years). The cysts had dense, necrotic surfaces with fibrous walls, eosinophilic and other inflammatory cell infiltrates, and frequent, persistent, bronchial connections. Sinusitis (9/9) and mastoiditis (3/4) were also observed radiographically.

Authors
Merten, DF; Buckley, RH; Pratt, PC; Effmann, EL; Grossman, H
MLA Citation
Merten, DF, Buckley, RH, Pratt, PC, Effmann, EL, and Grossman, H. "Hyperimmunoglobulinemia E syndrome: radiographic observations." Radiology 132.1 (July 1979): 71-78.
PMID
451223
Source
pubmed
Published In
Radiology
Volume
132
Issue
1
Publish Date
1979
Start Page
71
End Page
78
DOI
10.1148/132.1.71

Use of a human plaque-forming cell assay to study peripheral blood bursa-equivalent cell activation and excessive suppressor cell activity in humoral immunodeficiency.

A plaque assay that detects human mononuclear blood cells producing immunoglobulin (Ig)M antibody to sheep erythrocytes was investigated for its usefulness in studying B-cell activation and regulation in 24 patients with humoral immunodeficiency. Cells from 3 of 15 patients with common variable agammaglobulinemia produced some plaques (range 40--160/10(6) cells; normal range 80--1240/10(6)), but those from the other 12, from all 7 with x-linked agammaglobulinemia and from the 2 with x-linked immunodeficiency with hyper-IgM failed to produce any detectable plaques. In co-cultures of patient and normal cells a very good correlation was seen between results of the plaque assay and an IgM biosynthesis assay in detecting excessive suppressor cell activity. Cells from 7 of 15 common variable agammaglobulinemics, from 3 of 7 x-linked agammaglobulinemics, and from both patients with hyper-IgM caused significant suppression of IgM biosynthesis and(or) plaque formation by normal cells. The observations in the last two groups and discordance for excess suppressor activity in identical twins with common variable agammaglobulinemia suggest that the activity develops secondarily to whatever their primary defects may be. Culturing non-T cells from common variable agammaglobulinemics exhibiting excessive suppressor cell activity with normal T cells resulted in plaque formation in four of five patients so studied; in all five the suppressor activity was found in the T-cell population. The availability of a plaque assay for the study of blood cells from immunodeficient patients provides a new probe to examine the cellular nature of such defects.

Authors
Herrod, HG; Buckley, RH
MLA Citation
Herrod, HG, and Buckley, RH. "Use of a human plaque-forming cell assay to study peripheral blood bursa-equivalent cell activation and excessive suppressor cell activity in humoral immunodeficiency." J Clin Invest 63.5 (May 1979): 868-876.
PMID
376549
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
63
Issue
5
Publish Date
1979
Start Page
868
End Page
876
DOI
10.1172/JCI109386

In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients.

The cytotoxic nucleoside 2'-deoxyadenosine is excreted in excessive amounts by individuals with genetic deficiency of adenosine deaminase, and may be in part responsible for the severe combined immune dysfunction from which they suffer. Earlier studies from this laboratory showed that 2'-deoxyadenosine causes the irreversible inactivation of the enzyme S-adenosylhomocysteine hydrolase by an active site-directed, "suicide-like" process. In this communication we have demonstrated similar inactivation of S-adenosylhomocysteine hydrolase in hemolysate and in intact erythrocytes, as well as a striking deficiency of S-adenosylhomocysteine hydrolase activity in the erythrocytes of three adenosine deaminase-deficient patients. In vivo suicide-like inactivation of S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine may contribute to the cytotoxicity of 2'-deoxyadenosine and to the immune dysfunction in adenosine deaminase deficiency.

Authors
Hershfield, MS; Kredich, NM; Ownby, DR; Ownby, H; Buckley, R
MLA Citation
Hershfield, MS, Kredich, NM, Ownby, DR, Ownby, H, and Buckley, R. "In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients." J Clin Invest 63.4 (April 1979): 807-811.
PMID
312296
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
63
Issue
4
Publish Date
1979
Start Page
807
End Page
811
DOI
10.1172/JCI109367

Advances in asthma/allergy.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Advances in asthma/allergy." Pediatr Nurs 5.2 (March 1979): suppl B-D-.
PMID
254000
Source
pubmed
Published In
Pediatric Nursing
Volume
5
Issue
2
Publish Date
1979
Start Page
suppl B-D

Lymphocyte responses to ragweed antigens from different sources.

Authors
Ownby, DR; Buckley, RH
MLA Citation
Ownby, DR, and Buckley, RH. "Lymphocyte responses to ragweed antigens from different sources." J Allergy Clin Immunol 63.1 (January 1979): 65-66.
PMID
758341
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
63
Issue
1
Publish Date
1979
Start Page
65
End Page
66

Advances in asthma/allergy.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Advances in asthma/allergy." Pediatric nursing 5.2 (1979): suppl B-D. (Academic Article)
Source
manual
Published In
Pediatric Nursing
Volume
5
Issue
2
Publish Date
1979
Start Page
suppl B
End Page
D

Lymphocyte responses to pollen allergens: Cell requirements and responses to crude timothy and rye and purified rye antigens

Authors
Buckley, RH; Kardish, MB
MLA Citation
Buckley, RH, and Kardish, MB. "Lymphocyte responses to pollen allergens: Cell requirements and responses to crude timothy and rye and purified rye antigens." Journal of Allergy and Clinical Immunology 63.3 (1979): No.-16.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
63
Issue
3
Publish Date
1979
Start Page
No.
End Page
16

ELEVATED IMMUNOGLOBULIN IGA IN MILK FROM MOTHERS DELIVERING PRETERM INFANTS

Authors
GROSS, SJ; WAKIL, S; DAVID, RJ; FAIX, RG; BUCKLEY, RH
MLA Citation
GROSS, SJ, WAKIL, S, DAVID, RJ, FAIX, RG, and BUCKLEY, RH. "ELEVATED IMMUNOGLOBULIN IGA IN MILK FROM MOTHERS DELIVERING PRETERM INFANTS." PEDIATRIC RESEARCH 13.4 (1979): 449-449.
Source
wos-lite
Published In
Pediatric Research
Volume
13
Issue
4
Publish Date
1979
Start Page
449
End Page
449

CHILD WITH ASTHMA

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "CHILD WITH ASTHMA." DRUG THERAPY 9.4 (1979): 75-80.
Source
wos-lite
Published In
Drug therapy
Volume
9
Issue
4
Publish Date
1979
Start Page
75
End Page
80

Natural killing in immunodeficient patients.

Natural killing (NK) capacity was evaluated in peripheral blood mononuclear cells from 14 patients with well defined primary immunodeficiency disorders and compared with the activity of those cells in antibody-dependent cell-mediated cytotoxicity (ADCC) assays against antibody-coated erythrocyte (killed primarily by monocytes) and lymphoid or tumor targets (killed exclusively by lymphoid cells). A selective inability to lyse antibody-coated lymphocyte targets was observed with cells from patients with x-linked agammaglobulinemia, suggesting the involvement of either a different lymphocyte subpopulation or membrane receptor for NK and ADCC, or that a different functional susceptibility exists for the two types of killing. The only immunodeficiency state in which lymphocyte NK activity was found to be lacking was severe combined immunodediciency disease.

Authors
Koren, HS; Amos, DB; Buckley, RH
MLA Citation
Koren, HS, Amos, DB, and Buckley, RH. "Natural killing in immunodeficient patients." J Immunol 120.3 (March 1978): 796-799.
PMID
632589
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
120
Issue
3
Publish Date
1978
Start Page
796
End Page
799

Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up.

The clinical and immunologic features of 11 patients with transient hypogammaglobulinemia of infancy are reported and compared with those of the 16 patients previously reported. Seven were re-evaluated three to ten years after infancy. Two groups were identified: six who were found by screening relatives of patients with other types of immunodeficiency and five whose sera were sent because the patients were having frequent or unusual infections. Those in the first group had no significant health problems during early infancy or childhood. In the second group recurrent infection was a problem during early infancy but not in later years; the latter patients also frequently had other health problems. Serum immunoglobulin concentrations were entirely normal at the last evaluation in five of the six THI patients with immunodeficient relatives. In the second group, the concentrations of one or more immunoglobulin classes, although greatly increased, were still below the normal range. All 11 patients were found to be capable of synthesizing antibodies to human type A and B erythrocytes and to diphtheria and tetanus toxoids, usually by 6 to 11 months of age, and well before immunoglobulin concentrations became normal. Lymphocyte studies in vitro showed no abnormalities in the percentages of cells in the different subpopulations or in their responses to the mitogens. None of the patients was given immune serum globulin replacement therapy and none experienced serious infections during their period of follow-up. The finding of only 11 cases of THI among over 10,000 patients whose sera were sent for immunoglobulin studies over a 12-year period suggests that this is not a common entity.

Authors
Tiller, TL; Buckley, RH
MLA Citation
Tiller, TL, and Buckley, RH. "Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up." J Pediatr 92.3 (March 1978): 347-353.
PMID
632973
Source
pubmed
Published In
The Journal of Pediatrics
Volume
92
Issue
3
Publish Date
1978
Start Page
347
End Page
353

Antibody-dependent cellular cytotoxicity in primary immunodeficiency diseases and with normal leukocyte subpopulations. Importance of the type of target.

To gain insight into a possible role for antibody-dependent cell-mediated cytotoxicity in vivo, we examined the ability of leukocytes from 28 patients with primary immunodeficiency and from 20 normal controls to lyse three different types of antibody-coated targets in vitro. Mean cytotoxic indices +/-1 SD elicited by unfractionated mononuclear cells from normal controls were 28.74+/-13.26 for human HLA antibody-coated lymphocyte targets, 42.79+/-8.27 for rabbit IgG antibody-coated chicken erythrocyte targets, and 47.58+/-10.34 for human anti-CD (Ripley)-coated O+ erythrocyte targets. Significantly (P=<0.05) lower than normal mean cytotoxic indices against lymphocyte targets were seen with effector cells from 10 patients with X-linked agammaglobulinemia (3.7+/-4.33), in 10 with common variable agammaglobulinemia (16.05+/-7.74), in 3 with immunodeficiency with hyper IgM (18.41+/-4.88), and in 2 with severe combined immunodeficiency (3.94+/-0.3). Antibody-dependent cytotoxicity against chicken erythrocytes was significantly (P=<0.05) lower than normal only in the common variable agammaglobulinemic group (33.33+/-12.3) and against human erythrocytes only in the common variable (34.36+/-9.59) and hyper IgM (27.54+/-0.66) groups. Rosette and anti-F(ab')(2) depletion studies with normal leukocytes indicated that a nonadherent, nonphagocytic, non-Ig-bearing, non-C receptor-bearing, Fc receptor-bearing lymphocyte was the only effector capable of lysing HLA antiboyd-coated lymphocyte targets. Patients with infantile X-linked agammaglobulinemia and severe combined immunodeficiency appear to have a marked deficiency in this type of effector cell function.

Authors
Sanal, SO; Buckley, RH
MLA Citation
Sanal, SO, and Buckley, RH. "Antibody-dependent cellular cytotoxicity in primary immunodeficiency diseases and with normal leukocyte subpopulations. Importance of the type of target." J Clin Invest 61.1 (January 1978): 1-10.
PMID
618906
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
61
Issue
1
Publish Date
1978
Start Page
1
End Page
10
DOI
10.1172/JCI108907

Abnormalities in the regulation of human IgE synthesis.

Authors
Buckley, RH; Becker, WG
MLA Citation
Buckley, RH, and Becker, WG. "Abnormalities in the regulation of human IgE synthesis." Immunol Rev 41 (1978): 288-314. (Review)
PMID
360511
Source
pubmed
Published In
Immunological Reviews
Volume
41
Publish Date
1978
Start Page
288
End Page
314

Statement by the Executive Committee

Authors
Jr, TEVM; Buckley, RH; Bukantz, SC; Austen, KF; Reisman, RE; Freedman, SO; Bernstein, IL; rick, OLF; Patterson, R; Pearlman, DS; Slavin, RG
MLA Citation
Jr, TEVM, Buckley, RH, Bukantz, SC, Austen, KF, Reisman, RE, Freedman, SO, Bernstein, IL, rick, OLF, Patterson, R, Pearlman, DS, and Slavin, RG. "Statement by the Executive Committee." The Journal of Allergy and Clinical Immunology 62.2 (1978): 71--.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
62
Issue
2
Publish Date
1978
Start Page
71-

EVIDENCE FOR EXCESSIVE T SUPPRESSOR CELL ACTIVITY IN X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM

Authors
HERROD, HG; PERLMAN, DB; BUCKLEY, RH
MLA Citation
HERROD, HG, PERLMAN, DB, and BUCKLEY, RH. "EVIDENCE FOR EXCESSIVE T SUPPRESSOR CELL ACTIVITY IN X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM." PEDIATRIC RESEARCH 12.4 (1978): 480-480.
Source
wos-lite
Published In
Pediatric Research
Volume
12
Issue
4
Publish Date
1978
Start Page
480
End Page
480
DOI
10.1203/00006450-197804001-00707

FUNCTIONAL CHARACTERIZATION OF NATURAL KILLING AGAINST A MOUSE FIBROSARCOMA TARGET

Authors
BECKER, RL; BUCKLEY, RH
MLA Citation
BECKER, RL, and BUCKLEY, RH. "FUNCTIONAL CHARACTERIZATION OF NATURAL KILLING AGAINST A MOUSE FIBROSARCOMA TARGET." FEDERATION PROCEEDINGS 37.6 (1978): 1273-1273.
Source
wos-lite
Published In
The FASEB Journal
Volume
37
Issue
6
Publish Date
1978
Start Page
1273
End Page
1273

Anaphylactic reactions to plasma infusions in patients with hypogammaglobulinemia and anti-IgA antibodies.

Authors
Wells, JV; Buckley, RH; Schanfield, MS; Fudenberg, HH
MLA Citation
Wells, JV, Buckley, RH, Schanfield, MS, and Fudenberg, HH. "Anaphylactic reactions to plasma infusions in patients with hypogammaglobulinemia and anti-IgA antibodies." Clin Immunol Immunopathol 8.2 (September 1977): 265-271.
PMID
302773
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
8
Issue
2
Publish Date
1977
Start Page
265
End Page
271

Abnormalities of leukotaxis in atopic dermatitis.

Leukocyte chemotaxis studies were performed in 14 patients with atopic dermatitis. Monocyte chemotactic responsiveness (MCR), polymorphonuclear leukocyte (PMN) chemotactic responsiveness (PCR), and patient serum inhibition of normal monocyte chemotaxis were evaluated. The most common defect noted was depressed MCR. This was found in 8 of the 14 patients and was associated with a chemotactic inhibitor in the serum of 5 of 6 of the 8 with depressed MCR whose sera were so tested. Depressed PCR was found in 3 of 10 patients studied. Ten of the 14 patients had depressed chemotaxis of at least one cell type. Depressed chemotaxis was not related to the presence of infection, to the serum IgE level, or to the severity of the eczema, and it could not be produced in vitro by incubating normal cells with histamine or IgE myeloma. These studies demonstrate a high frequency of leukocyte chemotactic abnormalities in patients with severe atopic dermatitis. Elucidation of the clinical significance of the leukotactic abnormalities observed and determination of whether they are basic or secondary to the disease process must await further study.

Authors
Snyderman, R; Rogers, E; Buckley, RH
MLA Citation
Snyderman, R, Rogers, E, and Buckley, RH. "Abnormalities of leukotaxis in atopic dermatitis." J Allergy Clin Immunol 60.2 (August 1977): 121-126.
PMID
874212
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
60
Issue
2
Publish Date
1977
Start Page
121
End Page
126

Persistent and fatal central-nervous-system ECHOvirus infections in patients with agammaglobulinemia.

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.

Authors
Wilfert, CM; Buckley, RH; Mohanakumar, T; Griffith, JF; Katz, SL; Whisnant, JK; Eggleston, PA; Moore, M; Treadwell, E; Oxman, MN; Rosen, FS
MLA Citation
Wilfert, CM, Buckley, RH, Mohanakumar, T, Griffith, JF, Katz, SL, Whisnant, JK, Eggleston, PA, Moore, M, Treadwell, E, Oxman, MN, and Rosen, FS. "Persistent and fatal central-nervous-system ECHOvirus infections in patients with agammaglobulinemia." N Engl J Med 296.26 (June 30, 1977): 1485-1489.
PMID
301244
Source
pubmed
Published In
The New England journal of medicine
Volume
296
Issue
26
Publish Date
1977
Start Page
1485
End Page
1489
DOI
10.1056/NEJM197706302962601

HLA antigens in primary immunodeficiency diseases.

Authors
Buckley, RH; MacQueen, JM; Ward, FE
MLA Citation
Buckley, RH, MacQueen, JM, and Ward, FE. "HLA antigens in primary immunodeficiency diseases." Clin Immunol Immunopathol 7.3 (May 1977): 305-310.
PMID
872454
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
7
Issue
3
Publish Date
1977
Start Page
305
End Page
310

Immunoreconstitution.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Immunoreconstitution." Pediatr Clin North Am 24.2 (May 1977): 313-328. (Review)
PMID
323803
Source
pubmed
Published In
Pediatric Clinics of North America
Volume
24
Issue
2
Publish Date
1977
Start Page
313
End Page
328

Lymphocyte responses to purified ragweed allergens in vitro. I. Proliferative responses in normal, newborn, agammaglobulinemic, and atopic subjects

To evaluate cell mediated immune responsiveness to pollen allergens in atopic subjects, the authors studied the deoxyribonucleic acid (DNA) synthetic responses of their cultured lymphocytes to purified ragweed antigens E, K, and Ra 3. Since lymphocytes from some highly ragweed sensitive subjects gave poor proliferative responses when harvested on day 6, they undertook a series of dose response and time course studies in atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed sensitive atopic adults (8 immunotherapy treated, 11 untreated); 13 nonatopic controls; 4 newborns, and 9 agammaglobulinemic patients. The geometric mean of peak response counts per minute in all 45 subjects was 21,163 and in unstimulated cultures was 2,416 (p = < 0.0001). The mean day on which the maximal responses occurred was 8.7, and the mean dose eliciting the maximum responses was 59 μg/ml. Statistical comparisons of the stimulated culture data revealed no significant intergroup differences. The finding of vigorous responsiveness to these purified pollen allergens by lymphocytes from nonatopic normal, newborn, and agammaglobulinemic subjects suggests that ragweed pollen antigens are either ubiquitous and lead to cell mediated responsiveness in all subjects with intact cell mediated immunity, or that they may have mitogenic properties in addition to their known antigenic properties.

Authors
Buckley, RH; Seymour, F; Sanal, SO; Ownby, DR; Becker, WG
MLA Citation
Buckley, RH, Seymour, F, Sanal, SO, Ownby, DR, and Becker, WG. "Lymphocyte responses to purified ragweed allergens in vitro. I. Proliferative responses in normal, newborn, agammaglobulinemic, and atopic subjects." Journal of Allergy and Clinical Immunology 59.1 (January 1, 1977): 70-78.
Source
scopus
Published In
Journal of Allergy and Clinical Immunology
Volume
59
Issue
1
Publish Date
1977
Start Page
70
End Page
78
DOI
10.1016/0040-4020(76)80160-3

Lymphocyte responses to purified ragweed allergens in vitro. I. Proliferative responses in normal, newborn, agammaglobulinemic, and atopic subjects.

To evaluate cell-mediated immune responsiveness to pollen allergens in atopic subjects, we studied the deoxyribonucleic acid (DNA) synthetic responses of their cultured lymphocytes to purified ragweek antigens E, K, and Ra-3. Since lymphocytes from some highly ragweed-sensitive subjects gave poor proliferative responses when harvested on day 6, we undertook a series of dose-response and time-course studies in atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atop adults (8 immunotherapy treated, 11 untreated); 13 nonatopic controls; 4 newborns, and 9 agammaglobulinemic patients. The geometric mean of peak response counts per minute in all 45 subjects was 21,163 and in unstimulated cultures was 2,416 (p = less than 0.0001). The mean day on which the maximal responses occurred was 8.7, and the mean dose eliciting the maximum responses was 59 mug/ml. Statistical comparisons of the stimulated culture data revealed no significant intergroup differences. The finding of vigorous responsiveness to these purified pollen allergens by lymphocytes from nonatopic normal, newborn, and agammaglobulinemic subjects suggests that ragweed pollen antigens are either ubiquitous and lead to cell-mediated responsiveness in all subjects with intact cell-mediated inmunity, or that they may have miogenic properties in addition to their known antigenic properties.

Authors
Buckley, RH; Seymour, F; Sanal, SO; Ownby, DR; Becker, WG
MLA Citation
Buckley, RH, Seymour, F, Sanal, SO, Ownby, DR, and Becker, WG. "Lymphocyte responses to purified ragweed allergens in vitro. I. Proliferative responses in normal, newborn, agammaglobulinemic, and atopic subjects." J Allergy Clin Immunol 59.1 (January 1977): 70-78.
PMID
833376
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
59
Issue
1
Publish Date
1977
Start Page
70
End Page
78

Mitogen induced DNA synthetic responses of lymphocyte subpopulations in partial DiGeorge syndrome

Authors
Ownby, D; Herrod, H; Buckley, RH
MLA Citation
Ownby, D, Herrod, H, and Buckley, RH. "Mitogen induced DNA synthetic responses of lymphocyte subpopulations in partial DiGeorge syndrome." Clinical Research 25.1 (1977): 75A-.
Source
scival
Published In
Clinical Research
Volume
25
Issue
1
Publish Date
1977
Start Page
75A

ALOPECIA-AREATA, HYPOGAMMAGLOBULINEMIA, CONCANAVALIN A (CON A) HYPORESPONSIVENESS, AND AUTOIMMUNE HEMOLYTIC-ANEMIA

Authors
BECKER, WG; BUCKLEY, RH
MLA Citation
BECKER, WG, and BUCKLEY, RH. "ALOPECIA-AREATA, HYPOGAMMAGLOBULINEMIA, CONCANAVALIN A (CON A) HYPORESPONSIVENESS, AND AUTOIMMUNE HEMOLYTIC-ANEMIA." CLINICAL RESEARCH 25.1 (1977): A75-A75.
Source
wos-lite
Published In
Clinical Research
Volume
25
Issue
1
Publish Date
1977
Start Page
A75
End Page
A75

Successful pyrimethamine-sulfadiazine therapy of pneumocystis pneumonia in infants with X-linked immunodeficiency with hyper-IgM.

Authors
Whisnant, JK; Buckley, RH
MLA Citation
Whisnant, JK, and Buckley, RH. "Successful pyrimethamine-sulfadiazine therapy of pneumocystis pneumonia in infants with X-linked immunodeficiency with hyper-IgM." Natl Cancer Inst Monogr 43 (October 1976): 211-217.
PMID
1087957
Source
pubmed
Published In
National Cancer Institute monograph
Volume
43
Publish Date
1976
Start Page
211
End Page
217

Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings.

The hematologic and histologic features of two, nontwin, male siblings with severe combined immunodeficiency and variable granulocytopenia are compared to the four previously reported cases of reticular dysgenesis. These sibs died at 50 and 3 days of age, respectively, with Pseudomonas sepsis and congenital cytomegalovirus infection, respectively. A maternal uncle has selective IgA deficiency. Cord blood from the second sib contained a normal percentage of E-rosetting lymphocytes; however, these lymphocytes failed to respond to mitogenic stimulation in vitro. Erythrocyte and lymphocyte levels of adenosine deaminase were elevated in the father and the second sib. Serum immunoglobulin concentrations were low in both siblings.

Authors
Ownby, DR; Pizzo, S; Blackmon, L; Gall, SA; Buckley, RH
MLA Citation
Ownby, DR, Pizzo, S, Blackmon, L, Gall, SA, and Buckley, RH. "Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings." J Pediatr 89.3 (September 1976): 382-387.
PMID
956962
Source
pubmed
Published In
The Journal of Pediatrics
Volume
89
Issue
3
Publish Date
1976
Start Page
382
End Page
387

The functions and measurement of human B- and T-lymphocytes.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "The functions and measurement of human B- and T-lymphocytes." J Invest Dermatol 67.3 (September 1976): 381-390. (Review)
PMID
787433
Source
pubmed
Published In
Journal of Investigative Dermatology
Volume
67
Issue
3
Publish Date
1976
Start Page
381
End Page
390

Heterogeneity of lymphocyte subpopulations in severe combined immunodeficiency. Evidence against a stem cell defect.

Surface markers typical of T and B lymphocytes were present on varying proportions of peripheral blood lymphocytes from three infants with severe combined immunodeficiency disease. Despite this, functions mediated by T and B cells were either absent or very minimal in all three, including cell-mediated responses in vivo; the in vitro proliferative response to mitogens, allogeneic cells, or antigens; effector cell function in lymphocyte-antibody lymphocytolytic interaction assays; and in vitro synthesis of IgG, IgA, and IgM. In contrast, mononuclear cells from one of the infants were tested and found capable of lysing both human and chicken antibody-coated erythrocyte targets normally. Co-cultivation experiments with unrelated normal control lymphocytes failed to demonstrate suppressor cell activity for immunoglobulin synthesis in these infants. Augmentations of immunoglobulin production from 310 to 560% over that expected on the basis of individual culture data were noted in co-cultures of one of the infants' cells with two different unrelated normal control cells. These findings suggest that that infant may have had a T helper cell defect or that his T cells were unable to produce soluble factors necessary for B cell differentiation. The finding of cells with differentiation markers characteristic of T and B lymphocytes in each of these patients, though in variable quantities, is further evidence for heterogeneity among patients with the clinical syndrome of severe combined immunodeficiency and argues against the concept that their immunodeficiency was due to a stem cell defect.

Authors
Buckley, RH; Gilbertsen, RB; Schiff, RI; Ferreira, E; Sanal, SO; Waldmann, TA
MLA Citation
Buckley, RH, Gilbertsen, RB, Schiff, RI, Ferreira, E, Sanal, SO, and Waldmann, TA. "Heterogeneity of lymphocyte subpopulations in severe combined immunodeficiency. Evidence against a stem cell defect." J Clin Invest 58.1 (July 1976): 130-136.
PMID
1084354
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
58
Issue
1
Publish Date
1976
Start Page
130
End Page
136
DOI
10.1172/JCI108441

Correction of severe combined immunodeficiency by fetal liver cells.

As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.

Authors
Buckley, RH; Whisnant, KJ; Schiff, RI; Gilbertsen, RB; Huang, AT; Platt, MS
MLA Citation
Buckley, RH, Whisnant, KJ, Schiff, RI, Gilbertsen, RB, Huang, AT, and Platt, MS. "Correction of severe combined immunodeficiency by fetal liver cells." N Engl J Med 294.20 (May 13, 1976): 1076-1081.
PMID
3737
Source
pubmed
Published In
The New England journal of medicine
Volume
294
Issue
20
Publish Date
1976
Start Page
1076
End Page
1081
DOI
10.1056/NEJM197605132942002

Lymphocyte responses to antigen E in normal and in treated and untreated ragweed sensitive subjects

Authors
Buckley, RH; Sanal, SO; Ownby, DR
MLA Citation
Buckley, RH, Sanal, SO, and Ownby, DR. "Lymphocyte responses to antigen E in normal and in treated and untreated ragweed sensitive subjects." Journal of Allergy and Clinical Immunology 57.3 (1976): No.32-.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
57
Issue
3
Publish Date
1976
Start Page
No.32

FUNCTIONS AND MEASUREMENT OF HUMAN B-LYMPHOCYTES AND T-LYMPHOCYTES

Authors
BUCKLEY, RH
MLA Citation
BUCKLEY, RH. "FUNCTIONS AND MEASUREMENT OF HUMAN B-LYMPHOCYTES AND T-LYMPHOCYTES." JOURNAL OF INVESTIGATIVE DERMATOLOGY 67.3 (1976): 381-390.
Source
wos-lite
Published In
Journal of Investigative Dermatology
Volume
67
Issue
3
Publish Date
1976
Start Page
381
End Page
390
DOI
10.1111/1523-1747.ep12514711

OPTIMAL CONDITIONS TO AVOID SELECTIVE LOSSES OF T CELLS ON BOUYANT DENSITY GRADIENTS

Authors
BECKER, WG; BUCKLEY, RH
MLA Citation
BECKER, WG, and BUCKLEY, RH. "OPTIMAL CONDITIONS TO AVOID SELECTIVE LOSSES OF T CELLS ON BOUYANT DENSITY GRADIENTS." PEDIATRIC RESEARCH 10.4 (1976): 383-383.
Source
wos-lite
Published In
Pediatric Research
Volume
10
Issue
4
Publish Date
1976
Start Page
383
End Page
383

Inability of gestational hormones to account for the inhibitory effects of pregnancy plasmas on lymphocyte responses in vitro.

Authors
Schiff, RI; Mercier, D; Buckley, RH
MLA Citation
Schiff, RI, Mercier, D, and Buckley, RH. "Inability of gestational hormones to account for the inhibitory effects of pregnancy plasmas on lymphocyte responses in vitro." Cell Immunol 20.1 (November 1975): 69-80.
PMID
128418
Source
pubmed
Published In
Cellular Immunology
Volume
20
Issue
1
Publish Date
1975
Start Page
69
End Page
80

Depression of cell-mediated immunity in atopic eczema.

Prompted by recent observations that the thymus exerts an important regulatory influence over IgE antibody production in lower species, we conducted studies of immune function in 21 patients with atopic eczema to seek evidence for a similar relation in man. Skin tests for delayed hypersensitivity to Candida albicans and streptokinase-streptodornase (SK-SD) revealed a striking degree of anergy that correlated with the severity of the eczema. A correlation was also noted between the extent of the dermatitis and the magnitude of the serum IgE concentration. Other immunologic abnormalities did not appear related to the severity of eczema put pertained to the group as a whole. These included significantly (p = less than 0.0001) lower mean percentages of spontaneous sheep erythrocyte (E) or T cell rosettes and of rosettes with neuraminidase-treated sheep erythrocyte (En) rosettes, and significantly lower in vitro lymphocyte responsiveness of the mitogens concanavalin A (p = 0.0013) and poleweek mitogen (p = 0.0002) and to Candida antigen (p = 0.0017) than in normal subjects. Responses to phytohemagglutinin and tetanus toxoid were also depressed but differences were not statistically significant. An increased percentage (p = 0.0324) of peripheral blood B lymphocytes bearing the complement receptor was noted, but, except for a slight increase in lymphocytes bearing IgD, percentages of lymphocytes bearing other immunoglobulins (including IgE) were not elevated.

Authors
McGeady, SJ; Buckley, RH
MLA Citation
McGeady, SJ, and Buckley, RH. "Depression of cell-mediated immunity in atopic eczema." J Allergy Clin Immunol 56.5 (November 1975): 393-406.
PMID
810508
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
56
Issue
5
Publish Date
1975
Start Page
393
End Page
406

Iron deficiency anemia: its relationship to infection susceptibility and host defense.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Iron deficiency anemia: its relationship to infection susceptibility and host defense." J Pediatr 86.6 (June 1975): 993-995.
PMID
1127546
Source
pubmed
Published In
The Journal of Pediatrics
Volume
86
Issue
6
Publish Date
1975
Start Page
993
End Page
995

ENHANCED BACTERICIDAL ACTIVITY OF PHAGOCYTES FROM PATIENTS WITH CHRONIC GRANULOMATOUS DISEASE IN THE PRESENCE OF SULPHISOXAZOLE

The decrease in the frequency and severity of bacterial infections in four of five children with chronic granulomatous disease (C.G.D.) on long-term sulphonamide therapy was out of proportion to demonstrable direct antibacterial effects of the drug. In an attempt to determine the mechanism for this apparent protective effect, the killing of sulphisoxazole-resistant Escherichia coli and Staphylococcus aureus by leucocytes from five patients with C.G.D. was studied in the presence or absence of 5-50 μg. per ml. sulphisoxazole. With leucocytes from all five patients there was a modest but reproducible enhancement of bactericidal activity in the presence of the sulphonamide. Studies of phagocytosis-associated oxidative metabolism in patients' cells have not revealed a metabolic basis for improved killing. © 1975.

Authors
Johnston, R; Wilfert, C; Buckley, R; Webb, L; Dechatelet, L; Mccall, C
MLA Citation
Johnston, R, Wilfert, C, Buckley, R, Webb, L, Dechatelet, L, and Mccall, C. "ENHANCED BACTERICIDAL ACTIVITY OF PHAGOCYTES FROM PATIENTS WITH CHRONIC GRANULOMATOUS DISEASE IN THE PRESENCE OF SULPHISOXAZOLE." The Lancet 305.7911 (April 12, 1975): 824-827.
Source
scopus
Published In
The Lancet
Volume
305
Issue
7911
Publish Date
1975
Start Page
824
End Page
827
DOI
10.1016/S0140-6736(75)93002-0

Enhanced bactericidal activity of phagocytes from patients with chronic granulomatous disease in the presence of sulphisoxazole.

The decrease in the frequency and severity of bacterial infections in four of five children with chronic granulomatous disease (C.G.D.) on long-term sulphonamide therapy was out of proportion to demonstrable direct antibacterial effects of the drug. In an attempt to determine the mechanism for this apparent protective effect, the killing of sulphisoxazole-resistant Escherichia coli and Staphylococcus aureus by leucocytes from five patients with C.G.D. was studied in the presence or absence of 5-50 mug. per ml. sulphisoxazole. With leucocytes from all five patients there was a modest but reproducible enhancement of bactericidal activity in the presence of the sulphonamide. Studies of phagocytosis-associated oxidative metabolism in patients' cell have not revealed a metabolic basis for improved killing.

Authors
Johnston, RB; Wilfert, CM; Buckley, RH; Webb, LS; DcChatelet, LR; McCall, CE
MLA Citation
Johnston, RB, Wilfert, CM, Buckley, RH, Webb, LS, DcChatelet, LR, and McCall, CE. "Enhanced bactericidal activity of phagocytes from patients with chronic granulomatous disease in the presence of sulphisoxazole." Lancet 1.7911 (April 12, 1975): 824-827.
PMID
48055
Source
pubmed
Published In
The Lancet
Volume
1
Issue
7911
Publish Date
1975
Start Page
824
End Page
827

Serum IgD and IgE concentrations in immunodeficiency diseases.

Concentrations of IgD and IgE were measured in sera from 165 patients with well-defined immunodeficiency in an effort to find information possibly relevant to the roles of antibodies of these classes in host defense. Values for both immunoglobulins were generally quite low in patients who had marked deficiencies of all three major immunoglobulins, although occasional normal or high normal values for IgD were seen in hypogammaglobulinemic patients. Group mean IgD concentrations were also depressed in patients with Wiskott-Aldrich syndrome and in those with selective IgA deficiency; IgE concentrations were depressed in patients with X-linked immunodeficiency with hyper-IgM and in those with ataxia telangiectasia. IgD and IgE were both significantly elevated in patients with extreme hyperimmunoglobulinemia E and undue susceptibility to infection and in a patient with the Nezelof syndrome; none of these patients had histories suggestive of atopy. In addition, the mean IgE concentration was significantly elevated in patients with selective IgA deficiency, many of whom were atopic, and in those with the Wiskott-Aldrich syndrome. The highest IgD concentration (163 mg/100 ml) was found in serum from a boy with variable immunodeficiency who had a lifelong history of severe recurrent pharyngeal infections, primarily streptococcal in etiology. Recurrent staphylococcal infection was a feature common to many but not all patients with elevated serum IgE concentration. These data may prove useful in the future delineation of biologic roles for antibodies in these two immunoglobulin classes.

Authors
Buckley, RH; Fiscus, SA
MLA Citation
Buckley, RH, and Fiscus, SA. "Serum IgD and IgE concentrations in immunodeficiency diseases." J Clin Invest 55.1 (January 1975): 157-165.
PMID
803218
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
55
Issue
1
Publish Date
1975
Start Page
157
End Page
165
DOI
10.1172/JCI107906

Plasma therapy in immunodeficiency diseases.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Plasma therapy in immunodeficiency diseases." Birth Defects Orig Artic Ser 11.1 (1975): 347-351.
PMID
50097
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
11
Issue
1
Publish Date
1975
Start Page
347
End Page
351

Bone marrow and thymus transplantation in ataxia-telangiectasia.

Serum IgA concentrations were found to be normal in a boy with ataxia-telangiectasia and selective IgA deficiency several months after an infusion of bone marrow cells from an HL-A and MLR compatible normal sib. In addition, transient improvements were noted in both his in vivo and in vitro cellular immune responsiveness through the third month posttransplant. Despite this, no evidence of chimerism could be detected in karyotypic studies of his peripheral blood lymphocytes and bone marrow cells. No clinical or significant immunologic improvement was noted in his affected female sib following implantation of a fetal thymus or injection of transfer factor.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Bone marrow and thymus transplantation in ataxia-telangiectasia." Birth Defects Orig Artic Ser 11.1 (1975): 421-424.
PMID
125117
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
11
Issue
1
Publish Date
1975
Start Page
421
End Page
424

Clinical and immunologic features of selective IgA deficiency.

Selective absence of serum and secretory IgA is probably the most common form of human immunodeficiency. High frequencies of recurrent sinusitis, otitis media, pneumonia, and atopy were noted among a group of 75 such patients, all but 4 of whom were Caucasian. Seven instances of familial absence of IgA were detected among 106 relatives of 34 of the group; in 1 family 1 member from each of 3 successive generations was affected. Two IgA-deficient children were later found to have normal amounts of serum IgA. Despite their humoral deficit, B lymphocytes bearing surface IgA were detected in 9/9 IgA-deficient patients in immunofluorescence studies of their peripheral blood lymphocytes. Although in vitro lymphocyte responses to 2 putative T-cell mitogens and to allogenic cells were normal, results of spontaneous rosette formation studies with sheep erythrocytes raise the possibility of a lymphocyte subpopulation deficit in this condition.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Clinical and immunologic features of selective IgA deficiency." Birth Defects Orig Artic Ser 11.1 (1975): 134-142.
PMID
807270
Source
pubmed
Published In
Birth Defects: Original Article Series
Volume
11
Issue
1
Publish Date
1975
Start Page
134
End Page
142

Clinical immunology: meeting report of the committee on hospital based laboratory and clinical immunology of the American Association of Immunologists, 1975

Authors
Hess, EW; Reed, CE; Buckley, RH
MLA Citation
Hess, EW, Reed, CE, and Buckley, RH. "Clinical immunology: meeting report of the committee on hospital based laboratory and clinical immunology of the American Association of Immunologists, 1975." Journal of Immunology 115.2 (1975): 609-610.
Source
scival
Published In
Journal of Immunology
Volume
115
Issue
2
Publish Date
1975
Start Page
609
End Page
610

PROLONGED CNS VIRAL-INFECTION WITH ECHO 30 IN AN AGAMMAGLOBULINEMIC CHILD WITH INTACT CELL-MEDIATED-IMMUNITY

Authors
WHISNANT, JK; TREADWELL, EL; MOHANAKUMAR, T; WILFERT, CM; BUCKLEY, RH
MLA Citation
WHISNANT, JK, TREADWELL, EL, MOHANAKUMAR, T, WILFERT, CM, and BUCKLEY, RH. "PROLONGED CNS VIRAL-INFECTION WITH ECHO 30 IN AN AGAMMAGLOBULINEMIC CHILD WITH INTACT CELL-MEDIATED-IMMUNITY." PEDIATRIC RESEARCH 9.4 (1975): 336-336.
Source
wos-lite
Published In
Pediatric Research
Volume
9
Issue
4
Publish Date
1975
Start Page
336
End Page
336

CHRONIC GRAFT VERSUS HOST (G-V-H) DISEASE AFTER FETAL LIVER-TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY (SCID)

Authors
WHISNANT, JK; GILBERTSEN, RB; SCHIFF, RI; BUCKLEY, RH
MLA Citation
WHISNANT, JK, GILBERTSEN, RB, SCHIFF, RI, and BUCKLEY, RH. "CHRONIC GRAFT VERSUS HOST (G-V-H) DISEASE AFTER FETAL LIVER-TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY (SCID)." CLINICAL RESEARCH 23.1 (1975): A68-A68.
Source
wos-lite
Published In
Clinical Research
Volume
23
Issue
1
Publish Date
1975
Start Page
A68
End Page
A68

DEFECTS OF MONOCYTE CHEMOTAXIS IN PATIENTS WITH HYPERIMMUNOGLOBULINEMIA E AND UNDUE SUSCEPTIBILITY TO INFECTION

Authors
SNYDERMAN, R; BUCKLEY, RH
MLA Citation
SNYDERMAN, R, and BUCKLEY, RH. "DEFECTS OF MONOCYTE CHEMOTAXIS IN PATIENTS WITH HYPERIMMUNOGLOBULINEMIA E AND UNDUE SUSCEPTIBILITY TO INFECTION." CLINICAL RESEARCH 23.1 (1975): A25-A25.
Source
wos-lite
Published In
Clinical Research
Volume
23
Issue
1
Publish Date
1975
Start Page
A25
End Page
A25

FETAL LIVER-TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) - SUCCESS AND GRAFT VERSUS HOST (G-V-H) DISEASE

Authors
WHISNANT, JK; SCHIFF, RI; GILBERTSEN, RB; PLATT, MS; BUCKLEY, RH
MLA Citation
WHISNANT, JK, SCHIFF, RI, GILBERTSEN, RB, PLATT, MS, and BUCKLEY, RH. "FETAL LIVER-TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) - SUCCESS AND GRAFT VERSUS HOST (G-V-H) DISEASE." PEDIATRIC RESEARCH 9.4 (1975): 336-336.
Source
wos-lite
Published In
Pediatric Research
Volume
9
Issue
4
Publish Date
1975
Start Page
336
End Page
336

DEFECTS OF MONOCYTE CHEMOTAXIS IN PATIENTS WITH HYPERIMMUNOGLOBULINEMIA-E AND UNDUE SUSCEPTIBILITY TO INFECTION

Authors
SNYDERMAN, R; BUCKLEY, RH
MLA Citation
SNYDERMAN, R, and BUCKLEY, RH. "DEFECTS OF MONOCYTE CHEMOTAXIS IN PATIENTS WITH HYPERIMMUNOGLOBULINEMIA-E AND UNDUE SUSCEPTIBILITY TO INFECTION." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 55.2 (1975): 102-103.
Source
wos-lite
Published In
Journal of Allergy and Clinical Immunology
Volume
55
Issue
2
Publish Date
1975
Start Page
102
End Page
103

Combined immunodeficiency disease associated with adenosine deaminase deficiency. Report on a Workshop Held in Albany, New York, October 1, 1973

Fifty-five children with CID and known ADA status were studied at a Workshop held in Albany, New York. Erythrocyte ADA determinations were performed in 22 of the 55 patients, 13 of whom were ADA negative. The ADA defect appears to be transmitted as an autosomal recessive trait. Some patients with CID and ADA deficiency have characteristic radiologic abnormalities of the skeleton, which are not found in other illnesses. The thymus glands of all patients with CID and ADA deficiency who could be examined had evidence of thymic involution manifested by presence of Hassall's corpuscles and differentiated germinal epithelium; this is in contrast to "classic" thymus findings in CID with normal ADA. Adenosine deaminase probably plays an important, although as yet undefined, role in lymphocyte development and/or function. The deficiency of ADA in CID is the first enzyme defect observed in a deficiency disease of specific immunity. © 1975 The C. V. Mosby Company.

Authors
Meuwissen, HJ; Pollara, B; Pickering, RJ; Ammann, A; Biggar, D; Brunell, P; Buckley, R; Cohen, F; Cross, V; Dissing, J; Giblett, E; Griscelli, C; Hirschhorn, R; Hong, R; Huber, J; Keightley, R; Kersey, J; Koning, JD; Lischner, H; Los, W; Meuwissen, HJ; Moore, EC; Ochs, HD; Pachman, L; Parks, B; Rosen, F; Singer, D; South, MA; Wara, D; Wolfson, J; Meuwissen, HJ
MLA Citation
Meuwissen, HJ, Pollara, B, Pickering, RJ, Ammann, A, Biggar, D, Brunell, P, Buckley, R, Cohen, F, Cross, V, Dissing, J, Giblett, E, Griscelli, C, Hirschhorn, R, Hong, R, Huber, J, Keightley, R, Kersey, J, Koning, JD, Lischner, H, Los, W, Meuwissen, HJ, Moore, EC, Ochs, HD, Pachman, L, Parks, B, Rosen, F, Singer, D, South, MA, Wara, D, Wolfson, J, and Meuwissen, HJ. "Combined immunodeficiency disease associated with adenosine deaminase deficiency. Report on a Workshop Held in Albany, New York, October 1, 1973." The Journal of Pediatrics 86.2 (1975): 169-181.
PMID
1089440
Source
scival
Published In
The Journal of Pediatrics
Volume
86
Issue
2
Publish Date
1975
Start Page
169
End Page
181
DOI
10.1016/S0022-3476(75)80463-X

Precipitins to Candida albicans in chronic mucocutaneous candidiasis studied by crossed immunoelectrophoresis with intermediate gel. Correlation with clinical and immunological findings.

Authors
Axelsen, NH; Kirkpatrick, CH; Buckley, RH
MLA Citation
Axelsen, NH, Kirkpatrick, CH, and Buckley, RH. "Precipitins to Candida albicans in chronic mucocutaneous candidiasis studied by crossed immunoelectrophoresis with intermediate gel. Correlation with clinical and immunological findings." Clin Exp Immunol 17.3 (July 1974): 385-394.
PMID
4619788
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
17
Issue
3
Publish Date
1974
Start Page
385
End Page
394

Molecular form of adenosine deaminase in severe combined immunodeficiency.

Authors
Van der Weyden, MB; Buckley, RH; Kelley, WN
MLA Citation
Van der Weyden, MB, Buckley, RH, and Kelley, WN. "Molecular form of adenosine deaminase in severe combined immunodeficiency." Biochem Biophys Res Commun 57.3 (April 8, 1974): 590-595.
PMID
4827825
Source
pubmed
Published In
Biochemical and Biophysical Research Communications
Volume
57
Issue
3
Publish Date
1974
Start Page
590
End Page
595

Membrane receptors and in vitro responsiveness of lymphocytes in human immunodeficiency.

Authors
Schiff, RI; Buckley, RH; Gilbertsen, RB; Metzgar, RS
MLA Citation
Schiff, RI, Buckley, RH, Gilbertsen, RB, and Metzgar, RS. "Membrane receptors and in vitro responsiveness of lymphocytes in human immunodeficiency." J Immunol 112.1 (January 1974): 376-386.
PMID
4204605
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
112
Issue
1
Publish Date
1974
Start Page
376
End Page
386

Agammaglobulinemia, neutropenia, fever, and abdominal pain.

Authors
Buckley, RH; Rowlands, DT
MLA Citation
Buckley, RH, and Rowlands, DT. "Agammaglobulinemia, neutropenia, fever, and abdominal pain." J Allergy Clin Immunol 51.5 (May 1973): 308-318.
PMID
4697357
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
51
Issue
5
Publish Date
1973
Start Page
308
End Page
318

Plasma therapy in immunodeficiency diseases.

Authors
Buckley, RH
MLA Citation
Buckley, RH. "Plasma therapy in immunodeficiency diseases." Am J Dis Child 124.3 (September 1972): 376-381.
PMID
4538344
Source
pubmed
Published In
American Journal of Diseases of Children
Volume
124
Issue
3
Publish Date
1972
Start Page
376
End Page
381

Blocking of autologous and homologous leukocyte responses by human alloimmune plasmas: a possible in vitro correlate of enhancement.

Authors
Buckley, RH; Schiff, RI; Amos, DB
MLA Citation
Buckley, RH, Schiff, RI, and Amos, DB. "Blocking of autologous and homologous leukocyte responses by human alloimmune plasmas: a possible in vitro correlate of enhancement." J Immunol 108.1 (January 1972): 34-44.
PMID
5010395
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
108
Issue
1
Publish Date
1972
Start Page
34
End Page
44

Extreme hyperimmunoglobulinemia E and undue susceptibility to infection.

Authors
Buckley, RH; Wray, BB; Belmaker, EZ
MLA Citation
Buckley, RH, Wray, BB, and Belmaker, EZ. "Extreme hyperimmunoglobulinemia E and undue susceptibility to infection." Pediatrics 49.1 (January 1972): 59-70.
PMID
5059313
Source
pubmed
Published In
Pediatrics
Volume
49
Issue
1
Publish Date
1972
Start Page
59
End Page
70

Incompatible bone-marrow transplantation in lymphopenic immunologic deficiency. Circumvention of fatal graft-versus-host disease by immunologic enhancement.

Authors
Buckley, RH; Amos, DB; Kremer, WB; Stickel, DL
MLA Citation
Buckley, RH, Amos, DB, Kremer, WB, and Stickel, DL. "Incompatible bone-marrow transplantation in lymphopenic immunologic deficiency. Circumvention of fatal graft-versus-host disease by immunologic enhancement." N Engl J Med 285.19 (November 4, 1971): 1035-1042.
PMID
4937691
Source
pubmed
Published In
The New England journal of medicine
Volume
285
Issue
19
Publish Date
1971
Start Page
1035
End Page
1042
DOI
10.1056/NEJM197111042851901

Lymphopenic immunologic deficiency in identical twins: lymphocyte allografting and graft-versus-host disease following treatment with albumin-gradient-separated paternal bone marrow cells.

Authors
Buckley, RH; Kremer, WB; Rowlands, DT; Huntley, CC; Amos, DB; Huang, AT
MLA Citation
Buckley, RH, Kremer, WB, Rowlands, DT, Huntley, CC, Amos, DB, and Huang, AT. "Lymphopenic immunologic deficiency in identical twins: lymphocyte allografting and graft-versus-host disease following treatment with albumin-gradient-separated paternal bone marrow cells." Clin Exp Immunol 9.3 (September 1971): 289-304.
PMID
4398334
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
9
Issue
3
Publish Date
1971
Start Page
289
End Page
304

Serum immunogbulin cocentrations during normal pregnancy.

Authors
Marolis, GB; Buckley, RH; Younger, JB
MLA Citation
Marolis, GB, Buckley, RH, and Younger, JB. "Serum immunogbulin cocentrations during normal pregnancy." Am J Obstet Gynecol 109.7 (April 1, 1971): 971-976.
PMID
5549342
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
109
Issue
7
Publish Date
1971
Start Page
971
End Page
976

Serum IgE concentrations and skin reactivity to anti-IgE antibody in IgA-deficient patients.

Authors
Schwartz, DP; Buckley, RH
MLA Citation
Schwartz, DP, and Buckley, RH. "Serum IgE concentrations and skin reactivity to anti-IgE antibody in IgA-deficient patients." N Engl J Med 284.10 (March 11, 1971): 513-517.
PMID
5100722
Source
pubmed
Published In
The New England journal of medicine
Volume
284
Issue
10
Publish Date
1971
Start Page
513
End Page
517
DOI
10.1056/NEJM197103112841002

Characterization of precipitating antibodies to ruminant serum and milk proteins in humans with selective IgA deficiency.

Authors
Huntley, CC; Robbins, JB; Lyerly, AD; Buckley, RH
MLA Citation
Huntley, CC, Robbins, JB, Lyerly, AD, and Buckley, RH. "Characterization of precipitating antibodies to ruminant serum and milk proteins in humans with selective IgA deficiency." N Engl J Med 284.1 (January 7, 1971): 7-10.
PMID
4992076
Source
pubmed
Published In
The New England journal of medicine
Volume
284
Issue
1
Publish Date
1971
Start Page
7
End Page
10
DOI
10.1056/NEJM197101072840102

Evaluation of serum immunoglobulin concentrations in the perinatal period by use of a standardized method of measurement.

Authors
Buckley, RH; Younger, JB; Brumley, GW
MLA Citation
Buckley, RH, Younger, JB, and Brumley, GW. "Evaluation of serum immunoglobulin concentrations in the perinatal period by use of a standardized method of measurement." J Pediatr 75.6 (December 1969): 1143-1148.
PMID
4187141
Source
pubmed
Published In
The Journal of Pediatrics
Volume
75
Issue
6
Publish Date
1969
Start Page
1143
End Page
1148

Correlation of milk precipitins with IgA deficiency.

Authors
Buckley, RH; Dees, SC
MLA Citation
Buckley, RH, and Dees, SC. "Correlation of milk precipitins with IgA deficiency." N Engl J Med 281.9 (August 28, 1969): 465-469.
PMID
4183710
Source
pubmed
Published In
The New England journal of medicine
Volume
281
Issue
9
Publish Date
1969
Start Page
465
End Page
469
DOI
10.1056/NEJM196908282810903

Evaluation of serum immunoglobulin concentrations in the perinatal period by use of a standardized method of measurement

Concentrations of IgG, IgA, and IgM were quantitatively estimated by single radial diffusion in 133 maternal cord serum pairs and in 84 newborn sera. The antisera and reference standards were prepared in this laboratory and the IgM antibody-agar plates for cord and newborn sera contained the optimal amount of antiserum for IgM concentrations usually found at those ages. All data were converted to logarithms for statistical analyses. The ±2 standard deviation limits obtained for cord and newborn serum IgM concentrations were found to be sufficiently narrow to permit ready detection of deviations from the norm by standard statistical tests of significance. © 1969 The C. V. Mosby Company.

Authors
Buckley, RH; Younger, JB; Brumley, GW
MLA Citation
Buckley, RH, Younger, JB, and Brumley, GW. "Evaluation of serum immunoglobulin concentrations in the perinatal period by use of a standardized method of measurement." The Journal of Pediatrics 75.6 PART 2 (1969): 1143-1148.
Source
scival
Published In
The Journal of Pediatrics
Volume
75
Issue
6 PART 2
Publish Date
1969
Start Page
1143
End Page
1148

Serum immunoglobulins. II. Levels in children subject to recurrent infection.

Authors
Buckley, RH; Dees, SC; O'Fallon, WM
MLA Citation
Buckley, RH, Dees, SC, and O'Fallon, WM. "Serum immunoglobulins. II. Levels in children subject to recurrent infection." Pediatrics 42.1 (July 1968): 50-60.
PMID
4173091
Source
pubmed
Published In
Pediatrics
Volume
42
Issue
1
Publish Date
1968
Start Page
50
End Page
60

Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy.

Authors
Buckley, RH; Dees, SC; O'Fallon, WM
MLA Citation
Buckley, RH, Dees, SC, and O'Fallon, WM. "Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy." Pediatrics 41.3 (March 1968): 600-611.
PMID
4171004
Source
pubmed
Published In
Pediatrics
Volume
41
Issue
3
Publish Date
1968
Start Page
600
End Page
611

Hereditary alterations in the immune response: coexistence of "agammaglobulinemia", acquired hypogammaglobulinemia and selective immunoglobulin deficiency in a sibship.

Authors
Buckley, RH; Sidbury, JB
MLA Citation
Buckley, RH, and Sidbury, JB. "Hereditary alterations in the immune response: coexistence of "agammaglobulinemia", acquired hypogammaglobulinemia and selective immunoglobulin deficiency in a sibship." Pediatr Res 2.2 (March 1968): 72-84.
PMID
4174268
Source
pubmed
Published In
Pediatric Research
Volume
2
Issue
2
Publish Date
1968
Start Page
72
End Page
84
DOI
10.1203/00006450-196803000-00002

Defective cellular immunity associated with chronic mucocutaneous moniliasis and recurrent staphylococcal botryomycosis: immunological reconstitution by allogeneic bone marrow.

Authors
Buckley, RH; Lucas, ZJ; Hattler, BG; Zmijewski, CM; Amos, DB
MLA Citation
Buckley, RH, Lucas, ZJ, Hattler, BG, Zmijewski, CM, and Amos, DB. "Defective cellular immunity associated with chronic mucocutaneous moniliasis and recurrent staphylococcal botryomycosis: immunological reconstitution by allogeneic bone marrow." Clin Exp Immunol 3.2 (February 1968): 153-169.
PMID
4171049
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
3
Issue
2
Publish Date
1968
Start Page
153
End Page
169

Serum immunoglobulins. 3. Abnormalities associated with chronic urticaria in children.

Authors
Buckley, RH; Dees, SC
MLA Citation
Buckley, RH, and Dees, SC. "Serum immunoglobulins. 3. Abnormalities associated with chronic urticaria in children." J Allergy 40.5 (November 1967): 294-303.
PMID
5235204
Source
pubmed
Published In
The Journal of Allergy
Volume
40
Issue
5
Publish Date
1967
Start Page
294
End Page
303

Selective immunoglobulin deficiency associated with thymic alymphoplasia.

Authors
Buckley, RH; Bradford, WD; Butcher, SR
MLA Citation
Buckley, RH, Bradford, WD, and Butcher, SR. "Selective immunoglobulin deficiency associated with thymic alymphoplasia." Pediatrics 39.4 (April 1967): 506-515.
PMID
4164566
Source
pubmed
Published In
Pediatrics
Volume
39
Issue
4
Publish Date
1967
Start Page
506
End Page
515

The development of homologous skin-sensitizing antibodies in experimental thyroiditis.

Authors
Metzgar, RS; Buckley, RH
MLA Citation
Metzgar, RS, and Buckley, RH. "The development of homologous skin-sensitizing antibodies in experimental thyroiditis." Int Arch Allergy Appl Immunol 31.2 (1967): 174-183.
PMID
4960241
Source
pubmed
Published In
International Archives of Allergy and Applied Immunology
Volume
31
Issue
2
Publish Date
1967
Start Page
174
End Page
183

Nutritional and antigenic effects of two bovine milk preparations in infants.

Authors
Buckley, RH; Dees, SC
MLA Citation
Buckley, RH, and Dees, SC. "Nutritional and antigenic effects of two bovine milk preparations in infants." J Pediatr 69.2 (August 1966): 238-245.
PMID
4957771
Source
pubmed
Published In
The Journal of Pediatrics
Volume
69
Issue
2
Publish Date
1966
Start Page
238
End Page
245

Reactivity of Human IgG Antibodies in Primate and Guinea Pig Passive Anaphylaxis

Authors
Buckley, RH; Metzgar, RS
MLA Citation
Buckley, RH, and Metzgar, RS. "Reactivity of Human IgG Antibodies in Primate and Guinea Pig Passive Anaphylaxis." International Archives of Allergy and Immunology 29.5 (1966): 485-494.
Source
crossref
Published In
International archives of allergy and immunology
Volume
29
Issue
5
Publish Date
1966
Start Page
485
End Page
494
DOI
10.1159/000229732

The use of nonhuman primates for studies of reagin

The work of Layton6-11 demonstrating passive cutaneous anaphylaxis (PCA) in nonhuman primates with human atopic serum has been confirmed and expanded. The reaction appears to be a measure of reaginic activity; the sera from untreated atopic individuals utilized in these studies contained no detectable precipitating antibodies and no detectable tanned-cell antibodies to the antigen employed. Heating the sera to 56° C. for 1 hour destroyed their ability to produce PCA. The same immunoglobulin fraction, γ1A, believed to contain reaginic activity is implicated by these studies as responsible for producing PCA in nonhuman primates. PCA could not be produced with γ2 and γ1M immunoglobulin fractions from these same sera. There appears to be a difference between the sensitivity of the techniques of Prausnitz-Küstner and monkey PCA as a measure of reaginic activity, the P.K. technique manifesting greater sensitivity with the sera used in these studies. Both nonhuman primate PCA and P.K. exhibited the same specificity with the antigens used in these studies. Passive systemic anaphylaxis can also be produced in monkeys by intravenous sensitization with human atopic serum and with a fraction of this serum containing predominantly γ1A globulin. © 1965.

Authors
Buckley, RH; Metzgar, RS
MLA Citation
Buckley, RH, and Metzgar, RS. "The use of nonhuman primates for studies of reagin." Journal of Allergy 36.4 (1965): 382-396.
Source
scival
Published In
The Journal of Allergy
Volume
36
Issue
4
Publish Date
1965
Start Page
382
End Page
396
Show More

Research Areas:

  • Acute Disease
  • Adenosine Deaminase
  • Agammaglobulinemia
  • Age Factors
  • Aged
  • Allergens
  • Allergy and Immunology
  • Amino Acid Sequence
  • Antibodies
  • Antibodies, Anti-Idiotypic
  • Antibodies, Viral
  • Antibody Formation
  • Antibody Specificity
  • Antibody-Producing Cells
  • Antigen-Antibody Reactions
  • Antigen-Presenting Cells
  • Antigens, CD34
  • Antigens, CD40
  • Antigens, CD45
  • Antigens, Surface
  • Apoptosis
  • Asthma
  • Ataxia Telangiectasia
  • Australia
  • B-Lymphocytes
  • Blood
  • Blood Protein Disorders
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Brain
  • CD40 Ligand
  • CD8-Positive T-Lymphocytes
  • Candida albicans
  • Candidiasis
  • Cause of Death
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Membrane
  • Cerebrospinal Fluid
  • Child, Preschool
  • Chimera
  • Chimerism
  • Chromatography, Ion Exchange
  • Chromosome Deletion
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 4
  • Chronic Disease
  • Clinical Trial
  • Cohort Studies
  • Colon
  • Common Variable Immunodeficiency
  • Consanguinity
  • Cytokines
  • DNA
  • DNA Mutational Analysis
  • DNA Primers
  • DNA Transposable Elements
  • Databases, Factual
  • Dendritic Cells
  • Deoxyadenosines
  • DiGeorge Syndrome
  • Disease Susceptibility
  • Double-Blind Method
  • Duodenum
  • Echovirus 9
  • Echovirus Infections
  • Enterovirus B, Human
  • Esophagitis
  • Exons
  • Fatal Outcome
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Frameshift Mutation
  • Gastroesophageal Reflux
  • Gene Deletion
  • Gene Frequency
  • Gene therapy
  • Genes, Dominant
  • Genes, Recessive
  • Genetic Diseases, X-Linked
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Therapy
  • Genotype
  • Giardiasis
  • Goats
  • Graft Survival
  • Graft vs Host Disease
  • Granulocytes
  • Granulomatous Disease, Chronic
  • Growth
  • HLA Antigens
  • Haplotypes
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Herpesvirus 4, Human
  • Heterozygote Detection
  • Homozygote
  • Humans
  • Hypersensitivity
  • Hypersensitivity, Immediate
  • IgA Deficiency
  • Immune Adherence Reaction
  • Immune Sera
  • Immune System
  • Immune System Diseases
  • Immunity, Maternally-Acquired
  • Immunization, Passive
  • Immunocompromised Host
  • Immunodiffusion
  • Immunoenzyme Techniques
  • Immunoglobulin A
  • Immunoglobulin Class Switching
  • Immunoglobulin D
  • Immunoglobulin E
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Immunoglobulin M
  • Immunoglobulin mu-Chains
  • Immunoglobulins
  • Immunoglobulins, Intravenous
  • Immunologic Deficiency Syndromes
  • Immunologic Memory
  • Immunologic Techniques
  • Immunophenotyping
  • Immunotherapy
  • Incidence
  • Infant
  • Infant, Newborn
  • Infection
  • Infection Control
  • Injections, Intravenous
  • Interleukin-13
  • Interleukin-2
  • Interleukin-4
  • Intestine, Small
  • Janus Kinase 3
  • Kidney Neoplasms
  • Killer Cells, Natural
  • Lectins
  • Leiomyomatosis
  • Leukocytes
  • Leukocytes, Mononuclear
  • Liver Function Tests
  • Loss of Heterozygosity
  • Lymph Nodes
  • Lymphangiectasis, Intestinal
  • Lymphatic Diseases
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocytes
  • Lymphopenia
  • Lymphoproliferative Disorders
  • Major Histocompatibility Complex
  • Male
  • Maltose
  • Medical Records
  • Membrane Glycoproteins
  • Mice
  • Microfluidic Analytical Techniques
  • Middle Aged
  • Mitogens
  • Molecular Sequence Data
  • Monocytes
  • Multicenter Studies as Topic
  • Mutagenesis, Site-Directed
  • Mutation
  • Myelodysplastic Syndromes
  • Neonatal Screening
  • Neutrophils
  • Nucleoside Deaminases
  • Pediatrics
  • Pedigree
  • Phagocytes
  • Phenotype
  • Phytohemagglutinins
  • Pneumonia, Aspiration
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • Practice Guidelines as Topic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Prevalence
  • Prospective Studies
  • Protein-Tyrosine Kinases
  • RNA
  • RNA Splicing
  • RNA, Messenger
  • Rabbits
  • Radioimmunoassay
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-2
  • Receptors, Interleukin-7
  • Registries
  • Retreatment
  • Retrospective Studies
  • Rhinitis, Allergic, Seasonal
  • Rosette Formation
  • S-Adenosylhomocysteine
  • STAT6 Transcription Factor
  • Sequence Analysis, DNA
  • Serotherapy
  • Severe Combined Immunodeficiency
  • Sheep
  • Siblings
  • Signal Transduction
  • Skin Tests
  • Survival Analysis
  • Survival Rate
  • T-Lymphocytes
  • Thymus Gland
  • Tomography, X-Ray Computed
  • Trans-Activators
  • Transduction, Genetic
  • Transplantation Chimera
  • Transplantation Conditioning
  • Transplantation Immunology
  • Uniparental Disomy
  • United States
  • Unrelated Donors
  • Up-Regulation
  • Virus Diseases
  • Volunteers
  • Vomiting
  • Wiskott-Aldrich Syndrome
  • X Chromosome
  • Young Adult