HLA-DQ mismatches stimulate de novo donor specific antibodies in heart transplant recipients

The development of donor specific antibody is associated with graft rejection and increased mortality in solid organ transplant recipients. The majority of de novo donor specific antibodies (dnDSA) are against HLA-DQ antigens, but it has not been investigated if this is caused by more mismatches in the HLA-DQ locus between the recipient and donor. Here we examined the impact of HLA mismatches in eight HLA loci on the development of dnDSA and on rejection in a large cohort of heart transplant recipients. We evaluated HLA mismatches at the antigen level, the eplet level using HLAMatchmaker, and the epitope level using the PIRCHE algorithm. We found that the majority of dnDSA were against HLA-DQ antigens, and the number of dnDSA per mismatch is highest for HLA-DQ compared to other HLA loci. Furthermore, mismatches of HLA-DQ at the epitope level were associated with antibody-mediated rejection. Our results suggest that HLA mismatches at the HLA-DQ locus are more immunogenic than mismatches at other HLA loci to stimulate the development of dnDSA and to cause graft rejection.