title: The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness.
abstract: Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens.
  
  
  
  HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies.
  
  
  
  A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%.
  
  
  
  The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization.
authors.affiliation: Center for Clinical Transfusion Research.|Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.|Jon J. van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther P
authors.initials: EP
authors.lastname: Verduin
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.|Jon J. van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.affiliation: Center for Clinical Transfusion Research.|Jon J. van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leo M G
authors.initials: LM
authors.lastname: van de Watering
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Humphrey H H
authors.initials: HH
authors.lastname: Kanhai
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Center for Clinical Transfusion Research.|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
mesh_terms: D000906:Antibodies; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D012189:Retrospective Studies
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D059811:HLA-DRB1 Chains