The HLA‐DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness

BACKGROUND Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA‐DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3‐2.3). In this study we evaluated whether the HLA‐DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. STUDY DESIGN AND METHODS HLA‐DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. RESULTS A total of 3959 immunized patients (female‐to‐male ratio, 2.3) had been HLA‐DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2‐1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy‐induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1‐16) higher in those with multiple RBC antibodies and HLA‐PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. CONCLUSION The HLA‐DRB1*15 phenotype is associated with broad RBC and HLA immunization.