Bw4 and Bw6 are strongly immunogenic epitopes routinely assigned based on HLA-B typing results per Organ Procurement and Transplantation Network (OPTN) policies. These public epitopes and their variants are shared by some cross-reactive HLA-A and -C antigens. Although epitope mismatch has been associated with poor transplant outcomes, previous studies did not find such associations for Bw4/6 mismatch as defined by HLA-B antigens only. We hypothesized that a broader definition for Bw4/Bw6 mismatch that includes cross-reactive HLA-A and -C antigens may reveal the risk associated with these epitopes. In this retrospective cohort study, we examined kidney transplantations between 2000 and 2016 in the OPTN database and determined the association of Bw4/6 mismatch across all class I HLA antigens and renal graft outcomes. Even by this broader definition, Bw4/6 mismatch was not independently associated with 1-year graft rejection (adjusted OR: 0.99, 95%CI 0.93–1.06) or death-censored graft survival (adjusted HR: 1.02, 95%CI 1.00–1.05). There was no significant association among recipients who were already sensitized at transplant either. Our findings suggest that Bw4/6 mismatch alone is not associated with poor renal graft outcomes despite their strong immunogenicity, and the load of epitope mismatches over a certain threshold is likely required to cause adverse clinical consequences.

Bw4 和 Bw6 是根据器官采购和移植网络 (OPTN) 政策根据 HLA-B 分型结果常规分配的强免疫原性表位。这些公共表位及其变体由一些交叉反应性 HLA-A 和 -C 抗原共享。尽管表位错配与移植结果不佳有关，但先前的研究并未发现仅由 HLA-B 抗原定义的 Bw4/6 错配的这种关联。我们假设包括交叉反应性 HLA-A 和 -C 抗原在内的 Bw4/Bw6 错配的更广泛定义可能揭示与这些表位相关的风险。在这项回顾性队列研究中，我们在 OPTN 数据库中检查了 2000 年至 2016 年间的肾移植，并确定了所有 I 类 HLA 抗原的 Bw4/6 不匹配与肾移植结果的关联。即使按照这个更广泛的定义，Bw4/6 不匹配与 1 年移植排斥（调整后的 OR：0.99，95%CI 0.93-1.06）或死亡审查的移植物存活率（调整后的 HR：1.02，95%CI 1.00-1.05）无关。在移植时已经致敏的受者之间也没有显着关联。我们的研究结果表明，尽管 Bw4/6 错配具有很强的免疫原性，但单独的 Bw4/6 错配与不良的肾移植结果无关，并且表位错配的负载超过一定阈值可能会导致不良的临床后果。