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-DQA103:02-DQB103:03 dimer had the highest dnDSA formation rate of 28.3%. The HLA-DQA105:xx-DQB103:01 and HLA-DQA105:xx-DQB102:xx, which are known for their high immunogenicity in previous studies, showed a relatively low DSA formation rate of 4.3%. The common DQB101:xx-DQB105:xx and DQA101:xx-DQB106:xx dimers had DSA formation rates of 1.8% and 3.9%, respectively. The high immunogenic HLA-DQA103:02-DQB103:03 dimer formed haplotype with DRB109:01 (98%), whereas the low immunogenic HLA-DQA102:01-DQB103:03 dimer formed exclusively haplotype with DRB107:01.

CONCLUSIONS

The DQA103:02-DQB103:03 dimer and the HLA-DRB109:01-HLA-DQA103:02-DQB1*03:03 haplotype turned out to be the most immunogenic in inducing HLA-DQ dnDSA in this Northern Han Chinese cohort.