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在死者供肾分配中平衡公平性与人类白细胞抗原匹配以及表位错配

Balancing equity and human leukocyte antigen matching in deceased-donor kidney allocation with eplet mismatch.

作者信息

Mankowski Michal A, Gragert Loren, Keating Brendan, Lonze Bonnie E, Segev Dorry L, Montgomery Robert, Gentry Sommer E, Mangiola Massimo

机构信息

Transplant Institute, NYU Langone Health, New York, New York, USA; Department of Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, New York, USA.

Division of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.

出版信息

Am J Transplant. 2025 Jun;25(6):1226-1234. doi: 10.1016/j.ajt.2024.11.030. Epub 2024 Dec 2.

Abstract

Human leukocyte antigen-level matching in US kidney allocation has been deemphasized due to its role in elevating racial disparities. Molecular matching based on eplets might improve risk stratification compared to antigen matching, but the magnitude of racial disparities in molecular matching is not known. To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high-resolution allele-level human leukocyte antigen genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased-donor pool, we profiled the percentage of well-matched donors available for candidates by ethnicity. The prevalence of well-matched donors with 0-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates and 2-fold less for Latino candidates compared to 0-ABDR antigen mismatches. Compared to 0-DR antigen mismatch, 0-DR eplet mismatch was 1.33-fold more racially disparate for Asian and 1.28-fold more for Latino, with similar disparity for Black candidates, whereas 0-DQ eplet mismatch reduced disparities, showing 1.26-fold less disparity for Black, 1.14-fold less for Latino, but 1.26-fold higher for Asian candidates. The prevalence of well-matched donors for candidates of different ethnicities varied according to which molecules were chosen to define a low-risk match.

摘要

在美国肾脏分配中,人类白细胞抗原水平匹配因其在加剧种族差异方面的作用而不再受到重视。与抗原匹配相比,基于表位的分子匹配可能会改善风险分层,但分子匹配中种族差异的程度尚不清楚。为了明确地分配表位,我们利用了来自国家肾脏登记处的5193名具有高分辨率等位基因水平人类白细胞抗原基因型的个体队列。基于美国历史上已故捐赠者库的种族构成,使用重复随机抽样来模拟供体-受体基因型配对,我们按种族分析了可供候选人选择的匹配良好的供体百分比。与0-ABDR抗原错配相比,0-DR/DQ表位错配的匹配良好的供体在黑人候选人和亚洲候选人中的种族差异减少了3倍,在拉丁裔候选人中减少了2倍。与0-DR抗原错配相比,0-DR表位错配在亚洲人中的种族差异多1.33倍,在拉丁裔中多1.28倍,黑人候选人的差异相似,而0-DQ表位错配减少了差异,黑人的差异减少了1.26倍,拉丁裔减少了1.14倍,但亚洲候选人的差异增加了1.26倍。根据选择哪些分子来定义低风险匹配,不同种族候选人的匹配良好的供体患病率有所不同。

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