Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan.
Liver Transpl. 2021 Nov;27(11):1592-1602. doi: 10.1002/lt.26238. Epub 2021 Aug 23.
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.
人类白细胞抗原（HLA）分子错配（MM）分析可改善肾移植患者临床结局的预测，优于传统抗原 MM 预测。然而，HLA-DQB1 错配（DQB1-EpMM）水平是否可用于肝移植（LT）受者的风险分层仍不清楚。本研究回顾性观察了 45 例活体供肝 LT 患者，评估 Eplet MM 作为移植后 1 个月 T 细胞介导排斥反应（TCMR）和新的供体特异性抗体（dnDSA）形成的风险因素。共有 9 例（20%）患者发生 TCMR。HLA-A、HLA-B、HLA-C 和 HLA-DRB1 Eplet MM 数量与 TCMR 无关。相比之下，发生 TCMR 的患者 HLA-DQB1 Eplet MM（DQB1-EpMM）数量显著较高。HLA-DQB1 位点的预测间接可识别 HLA 表位（PIRCHE-II）评分（DQB1-PIRCHE-II）在 TCMR 组也显著高于无 TCMR 组。DQB1-EpMM≥7 或 DQB1-PIRCHE-II≥13 时，TCMR 发生的概率较高。移植前混合淋巴细胞反应分析表明，DQB1-EpMM 数量低（<7）和高（≥7）患者的抗供体 T 细胞增殖活性无显著差异。然而，增殖的抗供体 CD8 T 细胞上 CD25 表达的比例，作为细胞毒性活性标志物，在 DQB1-EpMM≥7 时较高。此外，DQB1-EpMM≥9 和 DQB1-PIRCHE-II≥3 都是 dnDSA 形成的预测因子。因此，MM 分析可根据个体风险进行个体化免疫抑制治疗。
