Determining Clinical Thresholds for Donor HLA Eplet Compatibility to Predict Best Outcomes Following Lung Transplantation

Steven J. Hiho, BSc; Duncan C. Walton, BSc; Miranda A. Paraskeva, MD; Bronwyn J. Levvey, RN; Mary B. Diviney, BSc; Gregory I. Snell, MD; Lucy C. Sullivan, PhD; Glen P. Westall, MD

doi:10.1097/TXD.0000000000001364

Transplantation Direct (Oct 2022)

Determining Clinical Thresholds for Donor HLA Eplet Compatibility to Predict Best Outcomes Following Lung Transplantation

Steven J. Hiho, BSc,
Duncan C. Walton, BSc,
Miranda A. Paraskeva, MD,
Bronwyn J. Levvey, RN,
Mary B. Diviney, BSc,
Gregory I. Snell, MD,
Lucy C. Sullivan, PhD,
Glen P. Westall, MD

Affiliations

Steven J. Hiho, BSc: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Duncan C. Walton, BSc: 3 Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Miranda A. Paraskeva, MD: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Bronwyn J. Levvey, RN: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Mary B. Diviney, BSc: 2 Australian Red Cross LifeBlood, Victorian Transplantation and Immunogenetics Service, Melbourne, VIC, Australia.
Gregory I. Snell, MD: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Lucy C. Sullivan, PhD: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Glen P. Westall, MD: 1 Lung Transplant Service, Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.

DOI: https://doi.org/10.1097/TXD.0000000000001364
Journal volume & issue: Vol. 8, no. 10
p. e1364

Abstract

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Background. Currently, the assessment of immunological risk in lung transplantation (LTx) does not completely consider HLA compatibility at the molecular level. We have previously demonstrated the association of HLA eplets in predicting chronic lung allograft dysfunction following LTx; however, the associations between HLA eplet mismatch (epMM) loads and overall survival are unknown. Methods. In this retrospective, single-center study, 277 LTx donor-recipient pairs were high resolution HLA typed and analyzed for HLA epMMs using HLAMatchmaker (version 3.1). LTx pairs were also assessed for the presence of the previously described risk epitope mismatches DQ2-DQA1*05 and DQ7-DQA1*05. Results. HLA class I epMMs were not associated with deleterious outcomes; however, lower HLA class II (≤19), DQA1 (≤2), and combined HLA class I and II (≤29) epMM demonstrated an association with increased time to chronic lung allograft dysfunction and improved overall survival. The presence of a risk epitope mismatch was not associated with worse clinical outcomes. Conclusions. HLA epMM can risk-stratify LTx recipients and potentially guide donor-recipient matching and immunosuppression strategies.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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