Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH, United States.
Department of Medicine and Public Health, University of Toledo, Toledo, OH, United States.
Front Immunol. 2022 Mar 24;13:832488. doi: 10.3389/fimmu.2022.832488. eCollection 2022.
Kidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients.
OPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations.
The retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0).
Race-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients.
肾脏移植在黑人患者中的失败率高于非黑人（白人、非黑人西班牙裔和亚洲人）患者。我们使用供体/受者 HLA 多态性氨基酸的估计物理化学免疫原性，为黑人患者选择免疫原性较弱的肾脏移植，与白人或非黑人患者进行比较。
使用 20 年期间的 65040 对供体/受者的数据，通过疏水、静电和氨基酸错配评分（HMS、EMS、AMS）计算个体物理化学免疫原性，并对黑人与白人或非黑人受者的移植物存活结果进行 Kaplan-Meier 生存和 Cox 回归分析。基于种族调整后的 HMS 阈值和临床可实现的分配，对受者与供者进行重新匹配的模拟。
黑人患者的回顾性中位肾脏移植物存活率为 12.0 年，白人患者为 18.6 年（6.6 年差异；p>0.001），非黑人患者为 18.4 年（6.4 年差异；p>0.01）。只有 0.7%的黑人患者接受了 HLA-A/B/DR/DQ 匹配（HMS=0）的移植，而白人患者为 8.1%（p<0.001）。在完全匹配的黑人患者（HMS=0）中，移植物存活率为 16.1 年，在匹配良好的黑人患者（HMS ≤ 3.0）中，移植物存活率为 14.0 年。白人患者在 HMS ≤ 3.0 时的存活率为 21.6 年，在 HMS ≤ 7.0 时为 18.7 年，而非黑人患者在 HMS ≤ 3.0 时的存活率为 22.0 年，在 HMS ≤ 7.0 时为 18.7 年，这证实了更高的 HMS 阈值可以产生优异的存活率。使用种族调整后的 HMS 阈值对 ABO 相容的供体-受者对进行模拟，确定了 HMS=0 时黑人患者的弱免疫原性匹配为 6.1%，HMS ≤ 3.0 时为 18.0%。尽管优先考虑黑人患者，但仍可以以与当前分配相同的水平匹配非黑人患者（HMS ≤ 7.0 时为 47.0%对 56.5%）。
基于种族调整的 HMS（EMS、AMS）分配增加了黑人患者的弱免疫原性供体数量，同时为非黑人患者提供了优异的选择。
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