Allan Kirk

Overview:

I am a surgeon with interest in immune management of transplant recipients. I am particularly interested in therapies that influence T cell costimulation pathways and adjuvant therapies that facilitate costimulation blockade to prevent the rejection of transplanted organs without undue suppression of protective immunity. I am also interested in understanding how injury, such as that occurring during trauma or in elective surgery, influences immune responses and subsequent healing following injury.

Positions:

David C. Sabiston, Jr. Distinguished Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Chair of Surgery

Surgery
School of Medicine

Professor in Pediatrics

Pediatrics
School of Medicine

Professor in the Department of Immunology

Immunology
School of Medicine

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1983

Old Dominion University

M.D. 1987

Duke University School of Medicine

Ph.D. 1992

Duke University

Intern & Junior Resident, Surgery

Duke University

Research Fellow, Surgery

Duke University

Senior Resident, Surgery

Duke University

Chief Resident, Surgery

Duke University

Fellow, Multi Organ Transplantation

University of Wisconsin - Madison

Grants:

Neonatal Porcine Islet Xenografts for the Treatment of Type 1 Diabetes

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Immune Tolerance Network - Flow Cytometry

Administered By
Surgery
Awarded By
Benaroya Research Institute at Virginia Mason
Role
Principal Investigator
Start Date
End Date

American Journal of Transplantation

Administered By
Surgery, Abdominal Transplant Surgery
Awarded By
American Society of Transplantation
Role
Principal Investigator
Start Date
End Date

Phase 2 Study of Belatacept, Alemtuzumab, and Sirolimus in Renal Transplantation

Administered By
Surgery
Awarded By
Food and Drug Administration
Role
Principal Investigator
Start Date
End Date

T cell Receptor Diversity as a Determinant of Co-stimulation Blockade Resistance

Administered By
Surgery
Awarded By
American Society of Transplant Surgeons
Role
Principal Investigator
Start Date
End Date

Publications:

The Legacy of Joseph A. Moylan, M.D.: "it's about Everyone Else"

The history of modern American surgery is marked by larger-than-life pioneers who have made transformative contributions to our field. These extraordinary individuals have been known primarily for their technical and clinical mastery, development of novel surgical procedures and techniques, extraordinary abilities in the education and training of surgeons, and/or innovative discoveries in biomedical science. While mastery in clinical surgery, education, and research have come to characterize the consummate academic surgeon, challenging social inequities of today now demand deeper engagement in another vital arena. This historical account is the story of a truly exceptional surgeon and visionary who spent much of his life leading that very charge. Early in his career, Dr. Joseph Moylan recognized and embraced this obligation to go beyond the walls of the hospital and out into the community to combat social factors leading to adverse outcomes for at-risk young men. His legacy itself represents a vehicle for empowering youth confronted with barriers to educational opportunities and experiences. Furthermore, recounting Joe's journey conveys the over-arching thesis that surgeons have the opportunity - and, indeed, are well positioned - to engage more deeply with their communities, to lead efforts to address social determinants at their roots and to create a pipeline of bright young scholars and potential future surgeons.
Authors
Mosca, PJ; Zani, S; Haglund, MM; Collins, BH; Wasiolek, S; Pappas, TN; Kirk, AD; Cendales, LC
MLA Citation
Mosca, P. J., et al. “The Legacy of Joseph A. Moylan, M.D.: "it's about Everyone Else".” Annals of Surgery, Jan. 2021. Scopus, doi:10.1097/AS9.0000000000000051.
URI
https://scholars.duke.edu/individual/pub1482748
Source
scopus
Published In
Annals of Surgery
Published Date
DOI
10.1097/AS9.0000000000000051

Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model.

Background: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA. Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression. Results: Circulating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (p<0.05), while using a DSA assay. T-cell flow cross match (TFXM) was reduced to 40.6±12.5% of baseline, and B-cell FXCM to 52.2±19.3%. Circulating total IgM and DSA IgM were unaffected by treatment. Pathogen-specific antibodies (anti-gB and anti-tetanus toxin IgG) were significantly reduced for 14d post infusion. Post-transplant, circulating IgG responded to anti-FcRn mAb treatment, but DSA increased rapidly. Conclusion: Targeting the FcRn-mediated recycling of IgG is an effective means of lowering circulating donor-specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remains unaffected.
Authors
Manook, M; Flores, WJ; Schmitz, R; Fitch, Z; Yoon, J; Bae, Y; Shaw, B; Kirk, A; Harnois, M; Permar, S; Farris, AB; Magnani, DM; Kwun, J; Knechtle, S
MLA Citation
Manook, Miriam, et al. “Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model.Front Immunol, vol. 12, 2021, p. 660900. Pubmed, doi:10.3389/fimmu.2021.660900.
URI
https://scholars.duke.edu/individual/pub1485996
PMID
34149698
Source
pubmed
Published In
Frontiers in Immunology
Volume
12
Published Date
Start Page
660900
DOI
10.3389/fimmu.2021.660900

Predicting the need for massive transfusion: Prospective validation of a smartphone-based clinical decision support tool.

BACKGROUND: Improper or delayed activation of a massive transfusion protocol may have consequences to individuals and institutions. We designed a complex predictive algorithm that was packaged within a smartphone application. We hypothesized it would accurately assess the need for massive transfusion protocol activation and assist clinicians in that decision. METHODS: We prospectively enrolled patients at an urban, level I trauma center. The application recorded the surgeon's initial opinion for activation and then prompted inputs for the model. The application provided a prediction and recorded the surgeon's final decision on activation. RESULTS: Three hundred and twenty-one patients were enrolled (83% male; 59% penetrating; median Injury Severity Score 9; mean base deficit -4.11). Of 36 massive transfusion protocol activations, 26 had an app prediction of "high" or "moderate" probability. Of these, 4 (15%) patients received <10 u blood as a result of early hemorrhage control. Two hundred and eighty-five patients did not have massive transfusion protocol activated by the surgeon with 27 (9%) patients having "moderate" or "high" likelihood predicted by the application. Twenty-four of these did not require massive transfusion, and all patients had acidosis that unrelated to hemorrhagic shock. For 13 (50%) of the patients with "high" probability, the surgeon correctly altered their initial decision based on this information. The algorithm demonstrated an adjusted accuracy of 0.96 (95% confidence interval [0.93-0.98); P ≤ .001]), sensitivity = 0.99, specificity 0.72, positive predictive value 0.96, negative predictive value 0.99, and area under the receiver operating curve = 0.86. CONCLUSION: A smartphone-based clinical decision tools can aid surgeons in the decision to active massive transfusion protocol in real time, although it does not completely replace clinician judgment.
Authors
Dente, CJ; Mina, MJ; Morse, BC; Hensman, H; Schobel, S; Gelbard, RB; Belard, A; Buchman, TG; Kirk, AD; Elster, EA
MLA Citation
Dente, Christopher J., et al. “Predicting the need for massive transfusion: Prospective validation of a smartphone-based clinical decision support tool.Surgery, vol. 170, no. 5, Nov. 2021, pp. 1574–80. Pubmed, doi:10.1016/j.surg.2021.04.034.
URI
https://scholars.duke.edu/individual/pub1484883
PMID
34112517
Source
pubmed
Published In
Surgery
Volume
170
Published Date
Start Page
1574
End Page
1580
DOI
10.1016/j.surg.2021.04.034

Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients.

Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the repopulating T cell kinetics in kidney transplant recipients who underwent alemtuzumab induction followed by belatacept/rapamycin-based immunosuppression over 36-month posttransplantation. We focused specifically on the correlation between repopulating T cell subsets and the age of patients. Substantial homeostatic Ki67-expressing T cell proliferation was seen posttransplantation. A repertoire enriched for naïve T (TNaïve ) cells emerged posttransplantation. Analysis by generalized estimating equation linear models revealed a strong negative linear association between reconstituting TNaïve cells and advancing age. A relationship between age and persistence of effector memory cells was shown. We assessed thymic output and found an increase in the frequency of recent thymic emigrants (RTEs, CD4+ CD31+ ) at 12-month posttransplantation. Patients under 30 years of age showed significantly higher levels of CD4+ CD31+ cells than patients over 55 years of age pre- and posttransplantation. IL-7 and autologous mature dendritic cells (mDCs) induced CD57- cell proliferation. In contrast, mDCs, but not IL-7, induced CD57+ cell proliferation. This study establishes the relationship between age and thymic output during T cell homeostatic repopulation after alemtuzumab induction. Trial Registration: ClinicalTrials.gov - NCT00565773.
Authors
Xu, H; Lee, H-J; Schmitz, R; Shaw, BI; Li, S; Kirk, AD
MLA Citation
Xu, He, et al. “Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients.Am J Transplant, vol. 21, no. 9, Sept. 2021, pp. 3163–74. Pubmed, doi:10.1111/ajt.16625.
URI
https://scholars.duke.edu/individual/pub1481704
PMID
33942491
Source
pubmed
Published In
Am J Transplant
Volume
21
Published Date
Start Page
3163
End Page
3174
DOI
10.1111/ajt.16625

Immune response profiling in patients with traumatic injuries associated with alcohol ingestion.

Traumatic injuries afflict more than 5 million people globally every year. Current and past animal research has demonstrated association among alcohol, trauma, and impaired immune function, whereas human registries have shown association between alcohol and morbidity as well as mortality. The purpose of this study is to elucidate the immune interactions with alcohol in traumatically injured patients. We prospectively enrolled 379 patients after trauma at three medical centers in the Surgical Critical Care Initiative. Plasma was analyzed using Luminex for up to 35 different cytokines. Collected samples were grouped by patients with detectable plasma alcohol levels versus those without. Univariate testing determined differences in analytes between groups. We built Bayesian belief networks with multiple minimum descriptive lengths to compare the two groups. All 379 patient samples were analyzed. Two hundred eighty-two (74.4%) patients were men, and 143 (37.7%) were White. Patients had a median intensive care unit length of stay (LOS) of 5.8 days and hospital LOS of 12 days. Using single variate analyses, eight different cytokines were differentially associated with alcohol. Cytokines IL-12 and IL-6 were important nodes in both models and IL-10 was a prominent node in the nonalcohol model. This study found select immune function differed between traumatically injured patients with measurable serum alcohol levels as compared with those without. Traumatically injured patients with positive blood alcohol content appear less able to inhibit inflammatory stress. Alcohol appears to suppress pro-inflammatory IL-12 and IL-6, whereas patients without alcohol have greater levels of anti-inflammatory IL-10 expressed at injury and may better regulate anti-inflammatory pathways. Future studies should determine the relationship with these markers with clinically oriented outcomes.
Authors
Breslin, AW; Limkakeng, AT; Silvius, E; Staton, CA; Almond, C; Joshi, M-B; Adams, B; Johnston, B; McGowan, L; Kirk, AD; Elster, E
MLA Citation
Breslin, Adam W., et al. “Immune response profiling in patients with traumatic injuries associated with alcohol ingestion.Clinical and Translational Science, vol. 14, no. 5, Sept. 2021, pp. 1791–98. Epmc, doi:10.1111/cts.13022.
URI
https://scholars.duke.edu/individual/pub1482100
PMID
33932089
Source
epmc
Published In
Clinical and Translational Science
Volume
14
Published Date
Start Page
1791
End Page
1798
DOI
10.1111/cts.13022