Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell–mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8⁺ T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.

中文翻译：

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分子错配预测活体肝移植后 T 细胞介导的排斥反应和新生供体特异性抗体的形成

与通过传统抗原 MM 进行预测相比，人类白细胞抗原 (HLA) 分子错配 (MM) 分析改善了肾移植临床结果的预测。然而，目前尚不清楚 MM 水平是否可用于肝移植 (LT) 受者的风险分层。对 45 名活体 LT 进行了回顾性观察研究，以评估 eplet MM 作为第一个月 T 细胞介导排斥反应 (TCMR) 和新生供体特异性抗体 (dnDSA) 形成的风险因素。共有 9 名 (20%) 患者显示 TCMR。HLA-A、HLA-B、HLA-C 和 HLA-DRB1 eplet MM 数量与 TCMR 无关。相比之下，TCMR 患者的 HLA-DQB1 eplet MM (DQB1-EpMM) 数量显着增加。TCMR 组中 HLA-DQB1 基因座 (DQB1-PIRCHE-II) 的预测间接可识别 HLA 表位 (PIRCHE-II) 评分也显着高于非 TCMR 组。DQB1-EpMM ≥ 7 或 DQB1-PIRCHE-II ≥ 13 时发生 TCMR 的可能性很高。移植前混合淋巴细胞反应分析表明，低数量（<7）和高数量（≥7）DQB1-EpMM 患者的抗供体 T 细胞增殖活性之间没有显着差异。然而，增殖抗供体 CD8 中 CD25 表达的比例 移植前混合淋巴细胞反应分析表明，低数量（<7）和高数量（≥7）DQB1-EpMM 患者的抗供体 T 细胞增殖活性之间没有显着差异。然而，增殖抗供体 CD8 中 CD25 表达的比例 移植前混合淋巴细胞反应分析表明，低数量（<7）和高数量（≥7）DQB1-EpMM 患者的抗供体 T 细胞增殖活性之间没有显着差异。然而，增殖抗供体 CD8 中 CD25 表达的比例⁺ T 细胞，用作细胞毒活性标记物，在 DQB1-EpMMs ≥ 7 中很高。此外，DQB1-EpMMs ≥9 和 DQB1-PIRCHE-II ≥3 都是 dnDSA 形成的预测因子。因此，MM 分析可应用于基于个体风险的定制免疫抑制。