Abstract
Red blood cell (RBC) transfusions are frequently required to treat patients with sickle cell disease (SCD) [1]. One of the most serious complications of repeat transfusion is alloimmunization to RBC antigens [2]. Because human leukocyte antigen (HLA) genes mediate the response to foreign antigens, particular HLA alleles may predispose to the development of alloimmunization in patients with SCD who receive multiple transfusions. We conducted a case-control study to determine if particular HLA alleles are associated with alloimmunization and whether HLA homozygosity influences the risk of developing RBC alloantibodies. High-resolution HLA genotyping was performed on DNA samples from 159 multiply transfused patients with SCD. HLA allele frequencies were compared between alloantibody-positive and alloantibody-negative groups. The HLA-DRB1 * 1503 allele was associated with an increased risk (P = 0.039), while HLA-DRB1 * 0901 conferred protection from alloimmunization (P = 0.008). HLA Class II locus homozygosity was more frequently observed in the alloantibody-negative group (P = 0.01). These preliminary findings suggest that particular HLA-DR81 alleles and overall homozygosity at HLA class II loci are associated with alloimmunization risk in SCD. If confirmed, HLA type may serve as a useful genetic predictor of alloimmunization risk, and permit a targeted approach to the use of phenotypically matched blood.
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