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HLA-DR/DQ eplet mismatch predicts de novo donor-specific antibody development in multi-ethnic Southeast Asian kidney transplant recipients on different immunosuppression regimens

Authors :
Emmett Tsz Yeung Wong
Denise Pochinco
Anantharaman Vathsala
Wee Kun Koh
Amy Lim
Hersharan Kaur Sran
Matthew Ross D’Costa
Zi Yun Chang
Peter W. Nickerson
Chris Wiebe
Source :
Frontiers in Genetics, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Eplet mismatch has been recognized as a more precise strategy for determining HLA compatibility by analyzing donor-recipient HLA differences at the molecular level. However, predicting post-transplant alloimmunity using single-molecule eplet mismatch categories has not been validated in Asian cohorts. We examined a cohort of Southeast Asian kidney transplant recipients (n = 234) to evaluate HLA-DR/DQ eplet mismatch as a predictor of de novo donor-specific antibody (dnDSA) development. HLA-DR/DQ single-molecule eplet mismatch was quantified using HLA Matchmaker, and we utilized previously published HLA-DR/DQ eplet mismatch thresholds to categorize recipients into alloimmune risk groups and evaluate their association with dnDSA development. Recognizing that the predominance of cyclosporine use (71%) may alter published eplet mismatch thresholds derived from a largely tacrolimus-based (87%) cohort, we evaluated cohort-specific thresholds for HLA-DR/DQ single-molecule eplet mismatch categories. Recipient ethnicities included Chinese (65%), Malays (17%), Indians (14%), and others (4%). HLA-DR/DQ dnDSA developed in 29/234 (12%) recipients after a median follow-up of 5.4 years, including against isolated HLA-DR (n = 7), isolated HLA-DQ (n = 11), or both (n = 11). HLA-DR/DQ single-molecule eplet mismatch risk categories correlated with dnDSA-free survival (p = 0.001) with low-risk recipients having a dnDSA prevalence of 1% over 5 years. The cohort-specific alloimmune risk categories improved correlation with HLA-DR/DQ dnDSA-free survival and remained significant after adjusting for calcineurin inhibitor and anti-metabolite immunosuppression (p < 0.001). We validated the performance of single-molecule eplet mismatch categories as a prognostic biomarker for HLA-DR/DQ dnDSA development in a cohort of predominantly Asian kidney transplant recipients after adjusting for different immunosuppression regimens.

Details

Language :
English
ISSN :
16648021
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.beae58e73fce47238a9c46082ee2aee4
Document Type :
article
Full Text :
https://doi.org/10.3389/fgene.2024.1447141