title: HLA-DRB1 associations in individuals with single and multiple clinically relevant red blood cell antibodies.
abstract: BACKGROUND
  A minority of red blood cell (RBC) alloantigen-exposed persons form antibodies. Responders are at high risk of developing additional antibodies upon subsequent transfusions. Several studies showed an association between particular HLA-DRB1 phenotypes and the development of specific RBC antibodies. This study evaluates the presence of HLA-DRB1 antigens in individuals with single or multiple RBC antibody specificities to explore whether the response against RBC antigens is associated with a summation of particular HLA-DRB1 susceptibility antigens.
  
  
  METHODS
  Frequencies of HLA-DRB1 alleles in individuals with antibodies against clinically relevant antigens were compared to a large population cohort to calculate odds ratios (ORs) for alloimmunization to different RBC antigens.
  
  
  RESULTS
  The study cohort consisted of 941 individuals (female-to-male ratio, 3.8) possessing 1462 antibody specificities elicited by transfusion, pregnancy, transplantation, or a combination of these. Besides confirmation of known associations, new associations were identified for anti-E with DRB1*09 and for anti-S with DRB1*07 (ORs, 3.7 and 8.7, respectively). Multiple antibody formation was in a minority of cases associated with the presence of multiple DRB1 susceptibility genes. In multiple responders DRB1*15 was present in almost 40% of cases compared to approximately 25% in single-antibody responders and in the control population.
  
  
  CONCLUSIONS
  This study suggests that HLA-DRB1 restriction plays an important role for a first RBC antibody response but multiple antibody formation seems less dependent on the presence of particular HLA restriction genes, while HLA-DRB1*15 may represent a susceptibility phenotype enhancing formation of multiple RBC antibody specificities.
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands; Jon J. van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Schonewille
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Wilfried H B M
authors.initials: WH
authors.lastname: Levering
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
mesh_terms: D001789:Blood Group Antigens / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000209:etiology / Q000235:genetics / Q000276:immunology; D001788:Blood Grouping and Crossmatching; D001803:Blood Transfusion; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D059811:HLA-DRB1 Chains / Q000032:analysis* / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000097:blood*; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D014181:Transplantation Immunology
chemical_list: D001789:Blood Group Antigens; D059811:HLA-DRB1 Chains; D007518:Isoantibodies; D007519:Isoantigens