D‐immunized blood donors who are female and who possess at least one HLA‐DRB115 allele show a propensity for high serum RhIG production

• Published in: Transfusion (Philadelphia, Pa.) Vol. 58; no. 5; pp. 1182 - 1188
• Main Authors: Tan, Joanne C.G., Yuan, Fang Fang, Daley, Jackie, Marks, Katherine, Flower, Robert L., Dyer, Wayne B.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2018
• Subjects: Alleles; Antigen presentation; Antigens; Biomarkers; Blood & organ donations; Blood Donors; Blood transfusion; CD14 antigen; Deoxyribonucleic acid; DNA; Drb1 protein; Erythrocytes; Female; Genetic factors; Genetic markers; Genetic Testing; Genotyping; Histocompatibility antigen HLA; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; Humans; Identification methods; Immunization; Immunogenicity; Major histocompatibility complex; Markers; Polymerase chain reaction; Receptors; Rh Isoimmunization; Rho(D) Immune Globulin - immunology; Sex; Sex Factors; Statistical analysis; Statistical tests; TLR2 protein; TLR4 protein; Toll-like receptors
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.14584

BACKGROUND D– individuals with previous D‐incompatible pregnancies and/or blood transfusions, as well as those who are actively immunized with small‐volume D+ red blood cells (RBCs), are stimulated to produce RhIG. Many factors could influence the stimulation of immunoglobulin production in response to foreign antigen (such as antigen immunogenicity and genetic factors), and it is unknown whether genetic markers could potentially identify responder anti‐D donors. STUDY DESIGN AND METHODS Anti‐D donors were assigned a responder profile based on their serum RhIG levels (n = 431). A subset of donors (n = 272) had DNA extracted for polymerase chain reaction genotyping assays for target genes in antigen presentation and pathogen recognition receptors (TLR2, TLR4, CD14, FcγRIIA, and the MHC Class II locus HLA‐DRB1). Statistical tests for associations between anti‐D donor responder profiles and genetic factors were performed. RESULTS A large proportion of our donors (38.7%) were classified as nonresponder donors, despite receiving multiple D+ RBC immunizations, whereas female sex was significantly associated with an all‐responder profile (p < 0.001). The presence of the DRB1*15 allele and absence of the DRB1*04 allele were more likely to be associated with a responder anti‐D donor, although not significantly after Bonferroni correction. A combination of the DRB1*15 allele and female sex was significantly associated with an anti‐D donor responder profile. CONCLUSION This study has identified female sex and the HLA‐DRB1*15 allele as potentially useful markers that could be used to screen donors before entry into D immunization programs.