Abstract
BACKGROUND: HLA-DQ antibodies are the most prevalent de novo donor-specific antibodies (dnDSAs) after kidney transplantation (KT). The immunogenicity and impact of each HLA-DQ mismatch on graft outcomes can vary considerably. METHODS: This retrospective cohort study investigated the prevalence and risk factors for dnDSA development in patients who underwent KT at Siriraj Hospital between 2006 and 2020 and had HLA-DQB1 mismatches. Our center employed a protocol for post-KT dnDSA surveillance. The impact of dnDSAs on late rejection and graft survival was evaluated. RESULTS: In our cohort of 491 KT recipients, 59 (12.02%) developed dnDSAs to HLA-DQB1 at a median time of 4.2 years after KT. The risk of dnDSA occurrence was significantly higher among recipients with HLA-DQ7 mismatch (HR: 2.8; 95% CI: 1.21-6.52; P = 0.017) and HLA-DQ9 mismatch (HR: 2.63; 95% CI: 1.11-6.27; P = 0.028). Recipients who developed dnDSAs were younger (P = 0.009), had higher rates of medication nonadherence (P = 0.031), had pre-KT panel reactive antibody levels above 20% (P = 0.044), and received non-tacrolimus immunosuppression (P < 0.001) compared to those without. Recipients who developed dnDSAs to HLA-DQ exhibited a significantly higher incidence of late graft rejection (HR: 7.76; 95% CI: 5-12.03; P < 0.0001) and inferior death-censored graft survival than those without dnDSAs (log rank P < 0.001). CONCLUSION: The patients with HLA-DQ7 and HLA-DQ9 mismatches exhibit the highest risk of developing dnDSAs. Individualized immunosuppression adjustment and kidney allocation based on specific HLA-DQ mismatch may enhance long-term graft survival.