Number of antibody-verified eplet in HLA-C locus as an independent factor of T-cell-mediated rejection after liver transplantation

Abstract

Background: HLA mismatching is a risk factor for graft rejection in solid organ transplantation. Its definition is being rethought with the introduction of the eplets in organ allocation. The eplets are highly polymorphic regions of the HLA molecule that help to explain cross-reactivity of HLA antigens. The effect of eplet mismatch is well documented in renal and lung transplantation but there is no clear evidence in liver transplantation. Methods: Forty-three consecutive liver-graft donor/recipient pairs performed at our center from 2016 to 2018 were HLA typed. The quantification of antibody-verified eplets (VerEp) mismatch was performed with HLA-matchmaker 2.1 version. Results: A total of 9 patients suffered an episode of T-cell-mediated rejection (TCMR). No significant differences were observed in the number of A, B, DRB, DQA, and DQB VerEp. However, the mean of mismatches VerEp in locus C (VerEpC) was significantly increased in patients with acute rejection: 3.89 (1.36) versus 2.32 (1.82), P = 0.021. A total of 22 patients with high load of VerEpC (>2) had an increased risk of TCMR (P = 0.008). The time of TCMR-free after liver transplant was statistically reduced in high-load VerEpC group (log-rank test P = 0.019). Multivariate analysis demonstrated that high load of VerEpC was independently associated with TCMR (P = 0.038). Conclusions: Patients with no or 1 eplet mismatch at the C locus are less likely to suffer TCMR after liver transplantation.