Background It remains unclear why only some patients form alloantibodies against foreign RBC antigens. Transfusion of red blood cell (RBC) products and pregnancy are the most relevant causes of immunization against RBC alloantigens. Here we investigated the relationship between RBC alloantibodies, Rh phenotype, and HLA phenotype among patients with multiple RBC alloantibodies Methods In a group of 124 multi-responders—including both pregnant women and transplant recipients—we analyzed the distribution of HLA-Class II variants in subgroups of multi-responders to RBC alloantigens according to their Rh status. Results As expected, the RhD-negative phenotype was overrepresented in our alloimmunized group (49.2%) compared to in the general population. Importantly, HLA-DRB1*15 carriers were significantly overrepresented among D-negative multi-responders compared to D-positive multi-responders (Pc = 0.045). Furthermore, the linked HLA-DRB1*13, HLA-DQB1*06, and HLA-DQA1*01 variants were more frequent in individuals with the DCCee phenotype than in other RhD-positive phenotypes. Conclusion Our present findings showed that RBC multispecific alloimmunization was associated with particular HLA-Class II variants based on Rh status.
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