Preformed Anti-DQ Alpha Donor-specific Antibodies and the Risk of Antibody-mediated Rejection After Kidney Transplantation

BACKGROUND: Anti-DQ donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection (AMR) after kidney transplantation, but previous studies focused on antibodies targeting the β-chain, neglecting the also polymorphic α-chain. METHODS: This study aimed to assess the frequency, characteristics, and pathogenicity of preformed anti-DQα DSAs in 2041 patients receiving a kidney transplant between 2010 and 2015 across 3 French transplantation centers. Donor and recipient 4-digit human leucocyte antigen typing and single-antigen bead mean fluorescence intensity data were compared with determine the specificity of anti-DQ antibodies. Associations between preformed anti-DQα DSAs and AMR were analyzed using Cox proportional hazard models. Patients with preformed anti-DQα DSAs were then matched to a control group of patients without preformed DSAs, to compare microvascular inflammation in 3-mo biopsies. RESULTS: After analysis of single-antigen bead data, we found that 122 kidney transplant recipients had preformed anti-DQα and anti-DQβ DSAs. Anti-DQα DSAs accounted for 35.2% of anti-DQ DSAs, with a median peak mean fluorescence intensity of 1331 (IQR 677-2896), targeting most frequently the DQA1*05 antigen (83.7%), and consistently the donor α/β heterodimer. In multivariable analyses, the presence of anti-DQα DSAs was associated with a higher risk of AMR, independently of DSAs targeting other loci (HR = 2.61; 95% CI, 1.31-6.01; P = 0.025). Moreover, patients with preformed anti-DQα DSAs had higher microvascular inflammation scores in their 3-mo biopsy than matched patients without DSAs (P < 0.001). CONCLUSIONS: Anti-DQα DSAs are independently associated with AMR after kidney transplantation, underscoring the importance of considering them in transplant allocation of and management of immunosuppression.