The optimal immunosuppression management in patients with a failed kidney transplant remains uncertain. This study analyzed the association of class II HLA eplet mismatches and maintenance immunosuppression with allosensitization after graft failure in a well characterized cohort of 21 patients who failed a first kidney transplant. A clinically meaningful increase in cPRA in this study was defined as the cPRA that resulted in 50% reduction in the compatible donor pool measured from the time of transplant failure until the time of repeat transplantation, death, or end of study. The median cPRA at the time of failure was 12.13% (interquartile ranges = 0.00%, 83.72%) which increased to 62.76% (IQR = 4.34%, 99.18%) during the median follow-up of 27 (IQR = 18, 39) months. High HLA-DQ eplet mismatches were significantly associated with an increased risk of developing a clinically meaningful increase in cPRA (p = 0.02) and de novo DQ donor-specific antibody against the failed allograft (p = 0.02). We did not observe these associations in patients with high HLA-DR eplet mismatches. Most of the patients (88%) with a clinically meaningful increase in cPRA had both a high DQ eplet mismatch and a reduction in their immunosuppression, suggesting the association is modified by immunosuppression. The findings suggest HLA-DQ eplet mismatch analysis may serve as a useful tool to guide future clinical studies and trials which assess the management of immunosuppression in transplant failure patients who are repeat transplant candidates.

中文翻译：

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HLA-DQ elet 错配和维持免疫抑制与肾移植失败后异体致敏风险的临床相关性

肾移植失败患者的最佳免疫抑制治疗仍不确定。本研究分析了 21 名首次肾移植失败患者的特征明确的队列，分析了 II 类 HLA eplet 错配和维持免疫抑制与移植失败后异体致敏的关系。本研究中具有临床意义的 cPRA 增加被定义为从移植失败时到重复移植、死亡或研究结束时测量的 cPRA 导致相容供体库减少 50%。失败时的中位 cPRA 为 12.13%（四分位距 = 0.00%、83.72%），在中位随访 27 次（IQR = 18、39）期间增加至 62.76%（IQR = 4.34%、99.18%）几个月。高 HLA-DQ eplet 错配与 cPRA (p = 0.02) 和针对失败同种异体移植物的 de novo DQ 供体特异性抗体 (p = 0.02) 产生有临床意义的增加的风险显着相关。我们没有在 HLA-DR elet 高度不匹配的患者中观察到这些关联。大多数 cPRA 有临床意义的增加的患者 (88%) 都具有较高的 DQ eplet 不匹配性和免疫抑制的减少，表明这种关联通过免疫抑制而改变。研究结果表明，HLA-DQ eplet 错配分析可作为指导未来临床研究和试验的有用工具，以评估重复移植候选人的移植失败患者的免疫抑制管理。