HLA-DQA1*03:02-DQB1*03:03 is the Dominant Immunogenic Heterodimer for Posttransplant HLA-DQ De Novo DSA Development in a Cohort of Chinese Kidney Transplant Patients

BACKGROUND: Eplets, acting as specificity determinants on donor HLA antigen molecules, may induce the formation of de novo donor-specific antibodies (dnDSAs) by the recipient's B cells posttransplantation. HLA-DQ DSAs are the most common type of DSAs that target mismatched donor HLA-DQ antigens. The HLA-DQ protein exists as a heterodimer, consisting of HLA-DQA1 and HLA-DQB1 molecules. The specific risk of each mismatched HLA-DQ dimer contributing to dnDSA formation remains underexplored. METHODS: A total of 434 kidney transplant donor/recipient pairs from Zheng Zhou University First Affiliated Hospital, who underwent the transplant procedure between September 2016 and November 2020, were included in this analysis. All were DSA-negative pretransplant. For each HLA-DQ heterodimer, the total incidence of dnDSA, alpha chain-specific dnDSA, and beta chain-specific dnDSA after kidney transplant was analyzed. The dnDSA formation rates of different mismatched HLA-DQ dimers were compared and their haplotype association with specific HLA-DRB1 protein were determined. RESULTS: In this study, 38 HLA-DQ dnDSAs were detected, with 28 to HLA-DQB1 and 10 to HLA-DQA1. HLA-DQA1*03:02-DQB1*03:03 dimer had the highest dnDSA formation rate of 28.3%. The HLA-DQA1*05:xx-DQB1*03:01 and HLA-DQA1*05:xx-DQB1*02:xx, which are known for their high immunogenicity in previous studies, showed a relatively low DSA formation rate of 4.3%. The common DQB1*01:xx-DQB1*05:xx and DQA1*01:xx-DQB1*06:xx dimers had DSA formation rates of 1.8% and 3.9%, respectively. The high immunogenic HLA-DQA1*03:02-DQB1*03:03 dimer formed haplotype with DRB1*09:01 (98%), whereas the low immunogenic HLA-DQA1*02:01-DQB1*03:03 dimer formed exclusively haplotype with DRB1*07:01. CONCLUSIONS: The DQA1*03:02-DQB1*03:03 dimer and the HLA-DRB1*09:01-HLA-DQA1*03:02-DQB1*03:03 haplotype turned out to be the most immunogenic in inducing HLA-DQ dnDSA in this Northern Han Chinese cohort.