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. STUDY DESIGN AND 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. CONCLUSION: 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.
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. STUDY DESIGN AND 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. CONCLUSION: 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: Seema R Patel; Ashley Bennett; Kathryn Girard-Pierce; Cheryl L Maier; Satheesh Chonat; Connie M Arthur; Patricia E Zerra; Amanda Mener; Sean R Stowell Journal: Blood Adv Date: 2018-01-23
Authors: Amanda Mener; Seema R Patel; Connie M Arthur; Satheesh Chonat; Andreas Wieland; Manjula Santhanakrishnan; Jingchun Liu; Cheryl L Maier; Ryan P Jajosky; Kathryn Girard-Pierce; Ashley Bennett; Patricia E Zerra; Nicole H Smith; Jeanne E Hendrickson; Sean R Stowell Journal: JCI Insight Date: 2018-11-15