Positive association of DRB1*04 and DRB1*15 alleles with Fy a immunization in a Southern European population

BACKGROUND: Anti‐Fy a has been implicated in hemolytic transfusion reactions. However, not all Fy(a−) patients develop anti‐Fy a after transfusion with 1 unit of blood [Fy(a+)]. This study was designed to identify HLA‐DRB1 alleles associated with a predisposition to Fy a immunization after blood transfusion. STUDY DESIGN AND METHODS: To identify HLA‐DRB1 alleles prone to immunization after blood transfusion or pregnancy, HLA‐DRB1 genotyping using polymerase chain reaction with sequence‐specific oligonucleotide nonradioactive probe/sequence‐specific priming methods was performed on blood samples from 67 immunized patients and 200 unrelated controls from the same southern European population in a case‐control retrospective study. RESULTS: Ninety‐six percent of patients with anti‐Fy a had at least one HLA‐DRB1 * 04 or HLA‐DRB1 * 15 allele compared to 34% of controls (p c  < 0.001). Furthermore HLA‐DRB1 * 04 and HLA‐DRB1 * 1501 frequencies were significantly increased in Fy a ‐immunized patients (35% vs. 12%, p c  < 0.001; and 30% vs. 19%, p c  < 0.001, respectively). Among HLA‐DRB1 * 04 allelic subtypes, DRB1 * 0401 and DRB1 * 0403 alleles were more strongly correlated with Fy a immunization (51% vs. 24% and 19% vs. 9%; p c  < 0.001, respectively). CONCLUSIONS: This study indicated that HLA‐DRB1 * 04 and DRB1 * 1501 are overrepresented in Fy a ‐immunized patients. The correlation between these alleles and Fy a immunization could be due to a particular presentation of the Fy a peptide in HLA‐DRB1 molecules.