在胰肾联合移植中，Eplet 错配评分与新生供者特异性抗体的产生。
Eplet mismatch scores and de novo donor-specific antibody development in simultaneous pancreas-kidney transplantation.
机构信息
Department of Surgery, Duke University, Durham, NC, USA; Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Histocompatibility and Immunogenetics Laboratory, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
出版信息
Hum Immunol. 2021 Mar;82(3):139-146. doi: 10.1016/j.humimm.2020.12.009. Epub 2020 Dec 31.
Antibody-mediated rejection is the principal cause of allotransplant graft failure. Available studies differ on the impact of de novo donor specific antibody (dnDSA) in pancreas transplants but are limited by patient sample size and sera sample collection. High-resolution HLA incompatibility scoring algorithms are able to more accurately predict dnDSA development. We hypothesized that HLA incompatibility scores as determined by the HLA-Matchmaker, HLA-EMMA, and PIRCHE-II algorithms would serve as a predictor of de novo donor specific antibody (dnDSA) development and clarify the role dnDSA as detrimental to simultaneous pancreas-kidney graft survival. Our results show that female sex and race were significantly associated with dnDSA development and dnDSA development resulted in worse kidney and pancreas graft survival. The majority of individuals who developed dnDSA (88%), developed anti-HLA-DQ antibody in some combination with anti-HLA class I or -DR. A multivariate analysis of the incompatibility scores showed that both HLA-Matchmaker and PIRCHE-II scores predicted anti-DQ dnDSA development. An optimal cutoff threshold for incompatibility matching was obtained for these scores and demonstrated statistical significance when predicting freedom from anti-DQ DSA development. In conclusion, increased scores from high-resolution HLA matching predict dnDSA development, and dnDSA is associated with antibody-mediated rejection and worse pancreas and kidney graft outcomes.
抗体介导的排斥反应是同种异体移植移植物失功的主要原因。现有研究对新诊断的供体特异性抗体（dnDSA）在胰腺移植中的影响存在差异，但受到患者样本量和血清样本采集的限制。高分辨率 HLA 不匹配评分算法能够更准确地预测 dnDSA 的发展。我们假设 HLA-Matchmaker、HLA-EMMA 和 PIRCHE-II 算法确定的 HLA 不匹配评分可作为新诊断的供体特异性抗体（dnDSA）发展的预测指标，并阐明 dnDSA 对同时胰腺-肾移植存活的有害作用。我们的研究结果表明，女性和种族与 dnDSA 发展显著相关，dnDSA 发展导致肾脏和胰腺移植物存活更差。大多数发展为 dnDSA 的个体（88%）以某种组合产生抗 HLA-DQ 抗体，同时伴有抗 HLA Ⅰ类或 -DR 抗体。对不匹配评分的多变量分析表明，HLA-Matchmaker 和 PIRCHE-II 评分均预测抗-DQ dnDSA 的发展。这些评分获得了不匹配匹配的最佳截断阈值，并在预测抗-DQ DSA 发展的自由时具有统计学意义。总之，高分辨率 HLA 匹配评分的增加预测 dnDSA 的发展，dnDSA 与抗体介导的排斥反应以及胰腺和肾脏移植物结局更差相关。
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