P215 Donor specific antibodies after transplantation: Importance of HLA-DQ

Abstract

Aim Development of de novo donor-specific HLA antibodies (DSA) after kidney and heart transplantation limits the long term success of this therapy and may lead to new transplantation. Luminex-supported single antigen bead assay (SAB) represents a major advantage in post-transplant monitoring by detecting different stages of antibody-mediated rejection (AMR). We aimed to explore the pattern of DSA generated after kidney and heart transplantation. Methods A total of 151 kidney and heart transplant recipients were tested from January in 2015. The sera collected at different time points after transplantation were screened for HLA-A, B, C, DR, DQ and DP specific antibodies by SAB (One Lambda). DSA positive patients and corresponding donors were additionally typed at high to intermediate level of resolution for antibody relevant loci. Screening results were analysed with HLA Fusion Software v3.4 at the allele and epitope level. Results DSA were detected in 32% of patients. Out of them 43% had class I and 82% class II DSA, respectively. The frequency of anti-DQ DSA (67%) were the highest of locus specific antibodies, moreover 39% of patients had anti-DQ DSA alone. Some of anti-DQ DSA were directed specifically at DQ-alpha, some at DQ-beta, and some at epitopes formed by amino acids from both chains. Our results confirmed that anti-DQ DSA recognize epitopes shared between different DQ molecules, mostly within broad serological specificities. For instance, in patients not carrying DQ3 and mismatched for DQ7, immune response was spread to DQ8 and DQ9 due to the epitope 55P on beta-chains coded from DQB1∗03:01, DQB1∗03:02 and DQB1∗03:03. Consequently, in the present allocation system all DQ3 molecules should be considered unacceptable for next transplantation. Conclusions Since epitope matching has not been implemented yet and anti-DQ specific antibodies are the predominant DSA after heart and kidney transplantation, full high to intermediate level of resolution DQ-alpha and -beta matching might be considered.