Parajuli Sandesh, Niemann Matthias, Dale Bethany L, Hidalgo Luis, Gupta Gaurav, Kaufman Dixon, Odorico Jon, Mandelbrot Didier
Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI.
PIRCHE AG, Berlin, Germany.
Transplant Direct. 2025 Feb 7;11(3):e1764. doi: 10.1097/TXD.0000000000001764. eCollection 2025 Mar.
Given the lack of specificity of current blood and urine testing and the resistance/inability to perform pancreas allograft biopsies, additional noninvasive investigational tools to assess the risk for rejection are needed. This study examines the clinical impact of molecular HLA matching in a large single-center simultaneous pancreas-kidney (SPK) transplant program.
The study cohort comprised 238 SPK recipients between 2012 and 2021. The number of HLA mismatches, eplet, Snow (that counts the number of protein-specific surface-accessible donor HLA amino acid mismatches), and predicted indirectly recognizable T-cell epitope (PIRCHE, version 4.2; 100%) loads were calculated on the basis of 2-field HLA-A, -B, -C, -DRB1, and -DQB1 typing of recipients and donors. Univariable and multivariable Cox proportional hazard, as well as Kaplan-Meier analyses, were performed considering either first rejection events of a graft or a composite endpoint of de novo donor-specific antibodies, first rejection, and uncensored graft failure of either organ.
Kaplan-Meier analyses considered class II PIRCHE groups separated by a threshold of 7. From the considered histocompatibility metrics, multivariable regression analysis revealed only PIRCHE-II derived from donor HLA class II as statistically significantly correlated with clinical events and rejection after SPK, mostly driven by pancreas rejections. Furthermore, longer dialysis time and the induction agent had significant negative impacts on the defined composite endpoint.
Our data support the clinical benefit of incorporating PIRCHE scores for the interpretation of class II HLA mismatches among patients undergoing SPK transplantation.
鉴于目前血液和尿液检测缺乏特异性，且难以进行胰腺移植活检，因此需要额外的非侵入性研究工具来评估排斥反应风险。本研究在一个大型单中心同期胰肾联合移植（SPK）项目中，探讨了分子 HLA 配型的临床影响。
研究队列包括 2012 年至 2021 年间的 238 例 SPK 受者。根据受者和供者的 HLA-A、-B、-C、-DRB1 和 -DQB1 的两字段分型，计算 HLA 错配数、表位、Snow（计算蛋白质特异性表面可及供者 HLA 氨基酸错配数）以及预测的间接可识别 T 细胞表位（PIRCHE，版本 4.2；100%）负荷。考虑移植物的首次排斥事件或新发供者特异性抗体、首次排斥以及任一器官的未删失移植物失败的复合终点，进行单变量和多变量 Cox 比例风险分析以及 Kaplan-Meier 分析。
Kaplan-Meier 分析考虑以 7 为阈值分隔的 II 类 PIRCHE 组。在所考虑的组织相容性指标中，多变量回归分析显示，仅源自供者 HLA II 类的 PIRCHE-II 与 SPK 后的临床事件和排斥反应在统计学上显著相关，主要由胰腺排斥反应驱动。此外，较长的透析时间和诱导剂对定义的复合终点有显著负面影响。
我们的数据支持在 SPK 移植患者中纳入 PIRCHE 评分以解释 II 类 HLA 错配的临床益处。
