Antibody-mediated rejection owing to donor-specific HLA-DQA1 antibodies after renal transplantation: A case report

Background: Donor-specific HLA antibodies are important risk factors in antibody-mediated rejection and graft loss after renal transplantation and are associated with higher rejection rates and lower graft survival. Most de novo donor specific antibodies (dnDSA) after renal transplantation are directed toward donor HLA-DQ antigens. An HLA-DQ antigen is a heterodimer consisting of an alpha and beta chain. Traditionally, HLA-DQA1 typing has not been part of pretransplant evaluation. Therefore, DQ alpha proteins are not usually considered in the interpretation of HLA-DQ antibody reactions. Methods: The renal transplant recipient had a 0% panel reactive antibody pretransplant. Two years after transplantation, he developed symptoms of abdominal distension and bilateral lower extremity edema. Histopathological findings on renal puncture biopsy showed a combination of T-cell-mediated acute rejection type IIA and antibody-mediated rejection with a trend toward chronicity in the transplanted kidney. DSAs were investigated by HLA-I (HLA-A/B) and HLA-II (HLA-DRB1/DQA1/DQB1) single antigen bead (SAB) assay. HLA typing was performed to explain the antibody reactivity patterns by PCR-SSO and Sequencing-based typing (SBT). HLA-Matchmaker analysis was performed to identify eplets that explain antibody reactivity patterns. Results: HLA-II SAB analysis of the patient's serum at the time of rejection showed positive reactions with all DQB1*03:03-carrying beads with high mean fluorescence intensity (MFI). However, DQB1*03:03 was not a dnDSA antigen. High-resolution HLA typing revealed that HLA-DQA1*05:01 and DQA1*03:02 were mismatched donor antigens. HLA Matchmaker analysis demonstrated reactivity toward 130R and 116 V eplet on DQA1 and DQB1. Conclusions: Antibodies specific to DQa chains after renal transplantation were highlighted.