Molecular mismatch predicts T cell mediated rejection and de novo donor specific antibody formation after living-donor liver transplantation.

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 transplant recipients. A retrospective observational study of 45 living-donor liver transplantations 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. Nine (20%) patients displayed TCMR. HLA-A, -B, -C, and -DRB1 eplet MM number was not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable human leukocyte antigen 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 DQB1-EpMM ≥7 or DQB1-PIRCHE-II ≥13. Pre-transplant mixed lymphocyte reaction analyses indicated that there were no significant differences between the anti-donor T-cell proliferation activities of patients with low-(<7) and high-number (≥7) DQB1-EpMM. However, the proportion of CD25 expression on proliferating anti-donor CD8+ T-cells, used as a cytotoxic activity marker, was high in DQB1-EpMM ≥7. Moreover, both DQB1-EpMM ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, molecular MMs analysis may be applied towards tailored immunosuppression based on individual risks. This article is protected by copyright. All rights reserved.