Susceptible and protective HLA-DR and HLA-DQ alleles for Fy a alloimmunization in the Croatian population.

BACKGROUND: Alloimmunization is a known risk of transfusion therapy caused by exposure to foreign RBC antigens. However, alloimmunization is not observed in all transfused patients. Human leukocyte antigen (HLA) molecules may contribute to the recognition and presentation of foreign antigens and to the potency of immune responses that result in the production of antibodies. The aim of this study was to determine the association of HLA-DR and HLA-DQ polymorphisms with alloimunization to Fya antigen in Croatian patients.

STUDY DESIGN AND METHODS: The study was conducted on 70 alloimmunized patients to Fya antigen and two control groups: 165 healthy Croatian individuals (Control 1) and 45 Fya antigen-negative nonimmunized patients exposed to Fya antigen (Control 2). Phenotype frequencies for HLA-DRB1 and HLA-DQB1 alleles were compared between the cases and control groups.

RESULTS: Statistically significant differences in phenotype frequencies between cases and controls were found for DRB1*04 (odds ratios [ORs], 10.5 and 18.7 for Control 1 and Control 2, respectively), DRB1*15 (ORs, 8.0 and 6.9), and DQB1*02 alleles (ORs, 0.2 and 0.03); and DRB1*04-DQB1*03:01 (ORs, 7.9 and 17.6), DRB1*04-DQB1*03:02 (ORs, 5.5 and 7.6), DRB1*15-DQB1*06:02 (ORs, 7.3 and 5.5), DRB1*03-DQB1*02:01 (OR, 0.1), and DRB1*07-DQB1*02:02 (OR, 0.3) haplotypes.

CONCLUSION: Several HLA-DRB1 and HLA-DQB1 alleles and haplotypes were proved to contribute to and protect from alloimmunization to Fya antigens. Alleles DRB1*04 and DRB1*15, as well as haplotypes DRB1*04-DQB1*03:02 and DRB1*15-DQB1*06:02 can be considered as risk factors, while allele DQB1*02 and haplotype DRB1*03-DQB1*02:01 have a protective role in Fya alloimmunization.