Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany.
PIRCHE AG, Berlin, Germany.
Front Immunol. 2021 Feb 26;12:631246. doi: 10.3389/fimmu.2021.631246. eCollection 2021.
We analyzed in a cohort of 68,606 first deceased donor kidney transplantations reported to the Collaborative Transplant Study whether an epitope-based matching of donor-recipient pairs using the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II) is superior to currently applied HLA antigen matching. PIRCHE-II scores were calculated based on split antigen HLA-A, -B, -DRB1 typing and adjusted to the 0-6 range of HLA mismatches. PIRCHE-II scores correlated strongly with the number of HLA mismatches (Spearman ρ = 0.65, < 0.001). In multivariable analyses both parameters were found to be significant predictors of 5-year death-censored graft loss with high prognostic power [hazard ratio (HR) per adjusted PIRCHE-II score = 1.102, per HLA mismatch = 1.095; -value PIRCHE-II: 9.8, HLA: 11.2; < 0.001 for both]. When PIRCHE-II scores and HLA mismatches were analyzed simultaneously, their predictive power decreased but remained significant (PIRCHE-II: = 0.002; HLA: < 0.001). Influence of PIRCHE-II was especially strong in presensitized and influence of HLA mismatches in non-sensitized recipients. If the level of HLA-incompatibility was low (0-3 mismatches), PIRCHE-II scores showed a low impact on graft survival (HR = 1.031) and PIRCHE-II matching did not have additional significant benefit ( = 0.10). However, if the level of HLA-incompatibility was high (4-6 mismatches), PIRCHE-II improved the positive impact of matching compared to applying the traditional HLA matching alone (HR = 1.097, = 0.005). Our results suggest that the PIRCHE-II score is useful and can be included into kidney allocation algorithms in addition to HLA matching; however, at the resolution level of HLA typing that is currently used for allocation it cannot fully replace traditional HLA matching.
我们在协作移植研究报告的 68606 例首次死亡供体肾移植队列中分析了，使用基于预测间接可识别 HLA 表位的算法（PIRCHE-II）进行供体-受者配对的表位匹配是否优于目前应用的 HLA 抗原匹配。PIRCHE-II 评分是基于分离抗原 HLA-A、-B、-DRB1 分型计算的，并调整到 HLA 错配的 0-6 范围。PIRCHE-II 评分与 HLA 错配数量密切相关（Spearman ρ=0.65，<0.001）。在多变量分析中，这两个参数均被发现是 5 年死亡 censored 移植物丢失的显著预测因子，具有较高的预后能力[每调整 PIRCHE-II 评分的风险比（HR）=1.102，每 HLA 错配=1.095；PIRCHE-II 值=9.8，HLA 值=11.2；均<0.001]。当同时分析 PIRCHE-II 评分和 HLA 错配时，其预测能力降低，但仍具有统计学意义（PIRCHE-II：=0.002；HLA：<0.001）。PIRCHE-II 的影响在致敏受者中尤为强烈，而 HLA 错配的影响在非致敏受者中更为强烈。如果 HLA 不匹配程度较低（0-3 个错配），则 PIRCHE-II 评分对移植物存活率的影响较小（HR=1.031），并且 PIRCHE-II 匹配没有额外的显著获益（=0.10）。但是，如果 HLA 不匹配程度较高（4-6 个错配），则 PIRCHE-II 提高了与单独应用传统 HLA 匹配相比匹配的积极影响（HR=1.097，=0.005）。我们的结果表明，PIRCHE-II 评分是有用的，可以与 HLA 匹配一起纳入肾脏分配算法中；但是，在目前用于分配的 HLA 分型分辨率水平上，它不能完全替代传统的 HLA 匹配。
