Susceptible and protective HLA‐DR and HLA‐DQ alleles for Fy^a alloimmunization in the Croatian population

Abstract

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.

Human Leucocyte Antigens in blood transfusion

“…A strong correlation between anti-Fy a alloimmunization and HLA-DRB1*04 and HLA-DRB1*15 genes, as well as with HLA-DRB1*04~DQB1*03 and HLA-DRB1*15~DQB1*06 haplotypes, was also observed [71,72]. In addition, the protective role of the HLA-DQB1*02 gene and DRB1*03~DQB1*02 and DRB1*07~DQB1*02 haplotypes for Fy a alloimmunization was also detected [72]. All presented data support the theory that the immunogenicity of a given RBC antigen is related both to the nature of the antigen and the capability of specific HLA class II molecules to present the derived peptides to T lymphocytes and initiate the immune response [23].…”

“…A study from the Czech population observed an association of HLA‐DRB1*15 and DQB1*06 genes with RBC antibody multiresponder status, but also an association of three frequent antibody combinations (anti‐C+D, anti‐E+c and anti‐E+Cw) and HLA‐DRB1 genes (HLA‐DRB1*15, HLA‐DRB1*13 and HLA‐DRB1*03, respectively) . A strong correlation between anti‐Fy a alloimmunization and HLA‐DRB1*04 and HLA‐DRB1*15 genes, as well as with HLA‐DRB1*04~DQB1*03 and HLA‐DRB1*15~DQB1*06 haplotypes, was also observed . In addition, the protective role of the HLA‐DQB1*02 gene and DRB1*03~DQB1*02 and DRB1*07~DQB1*02 haplotypes for Fy a alloimmunization was also detected .…”

Association of multispecific red blood cell alloimmunization with HLA-Class II variants is related to Rh phenotypes

“…In this study, we investigated the distribution of HLA-Class II variants within subgroups of multi-responders to RBC alloantigens, with the aim of elucidating associations between HLA-Class II alleles, Rh phenotypes, and RBC alloimmunization. In the previous studies, HLA-DRB1*15 has been associated with multiple RBC antibody responsiveness (13)(14)(15) and with anti-Fy a alloimmunization (10,11,16). Here we found that the DRB1*15 variant was twice as frequent in multi-responders with the D-negative phenotype as in RhD-positive multi-responders.…”

HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta‐analysis)

“…Similarly, Baleotti et al [21] had concluded that there was an overrepresentation of HLA-DRB1*07 in patients alloimmunized with anti-Di a compared to non-alloimmunized patients, 75% and 27%, respectively. both) [19,37].…”

“…A relationship between HLA polymorphisms and immune responses to various RBC antigens has been established, and these include Duffy a [ 18 , 19 ], Kell [ 20 ], Diego [ 21 ] and Kidd a [ 22 ]. Noizait‐Pirenne et al conducted a study to identify the HLA‐DRB1 restriction molecules within the anti‐Fy a and anti‐K groups in Caucasians.…”