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

被引:1
|
作者
Wong, Emmett Tsz Yeung [1 ,2 ,3 ]
Pochinco, Denise [4 ]
Vathsala, Anantharaman [1 ,2 ]
Koh, Wee Kun [2 ]
Lim, Amy [2 ]
Sran, Hersharan Kaur [1 ,2 ]
D'Costa, Matthew Ross [2 ]
Chang, Zi Yun [2 ]
Nickerson, Peter W. [3 ,4 ,5 ]
Wiebe, Chris [3 ,4 ,5 ]
机构
[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore
[2] Natl Univ Singapore Hosp, Natl Univ Ctr Organ Transplantat, Singapore, Singapore
[3] Univ Manitoba, Dept Med, Winnipeg, MB, Canada
[4] Shared Hlth Serv Manitoba, Winnipeg, MB, Canada
[5] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada
关键词
human leukocyte antigen; histocompatibility; molecular mismatch; eplets; kidney transplant; donor-specific antibodies; MEDIATED REJECTION; EPITOPE-MISMATCH; FAILURE; RISK;
D O I
10.3389/fgene.2024.1447141
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:9
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