Donor-Specific Antibodies Targeting a Repeated Eplet Mismatch and Outcome After Kidney Retransplantation.

Abstract

Kidney retransplantations are associated with an increased risk of rejection and reduced graft survival compared to first transplantations, notably due to HLA sensitization. The impact of repeated eplet mismatches on retransplantation outcome has not been investigated. We retrospectively assessed the risk of antibody-mediated rejection (ABMR) and graft loss associated with preformed DSA targeting Repeated Eplet MisMatches (DREMM) in sensitized patients undergoing kidney retransplantation. We included 45 retransplanted patients with preformed DSA against the second donor. We determined HLA incompatibilities at the eplet levels, and the eplet target of the DSA using HLAMatchmaker^®. Repeated mismatches were more frequent at the eplet (87%) than at the antigenic level (22%), but were not associated with the risk of ABMR. The eplet specificity of the DSA revealed that 60% of patients (n = 27) had DREMM. The presence of DREMM was associated with a higher frequency of ABMR (70% versus 28%, P = 0.005) and with a lower death-censored graft survival (log-rank test, P = 0.01). However, in multivariate Cox model, we could not show that DREMM were associated with the risk of ABMR. In conclusion, this study suggests that identifying DREMM may be an interesting clinical tool, however further larger studies are necessary to precise their exact predictive value.