De novo donor-specific HLA antibodies (DSA) have been recognized over the past several years as being the leading cause of late renal allograft failure. De novo DSA posttransplant result from HLA mismatches under the impact of inadequate immunosuppression. Determinants of DSA specificity are generated via the indirect allorecognition pathway. We investigated the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict the development of de novo DSA following kidney transplantation.
In this study which was conducted jointly with the Charité Universitätsmedizin Berlin, a total of 2,787 consecutive kidney transplants performed between 1995 and 2015 were enrolled. All patients revealed having no DSA prior to transplant as detected by solid-phase immunoassays. Posttransplant de novo DSA were detected by the Luminex® single antigen assay. HLA epitope mismatches were determined by both the Matchmaker and PIRCHE approach. Therefore, high resolution HLA typing was estimated from National Marrow Donor Program haplotype frequencies. The count of epitope mismatches and the classical antigen mismatches were correlated in uni- and multivariate analyses with renal allograft survival and the incidence of de novo DSA.
The study results confirmed previous findings on the PIRCHE score as a strong predictive measure for allorecognition following transplantation. PIRCHE score independently from antigen mismatch and Matchmaker epitopes could be revealed as having a strong predictive value for de novo DSA. Therefore, the PIRCHE score could help to identify acceptable mismatches with relatively reduced risk for development of de novo DSA and thus improve long-term renal allograft survival.
