Red blood cell minor antigen mismatches during chronic transfusion therapy for sickle cell anemia

• Type of Material: Article
• Authors: Marianne Yee, Emory University; Cassandra D Josephson, Emory University; Anne M. Winkler, Emory University; Jennifer Webb, George Washington University; Naomi L.C. Luban, George Washington University; Traci Leong, Emory University; Sean R. Stowell, Emory University; Ross M. Fasano, Emory University
• Language: English
• Date: 2017-11-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 AABB
• Final Published Version (URL): http://dx.doi.org/10.1111/trf.14282
• Title of Journal or Parent Work: Transfusion
• ISSN: 0041-1132
• Volume: 57
• Issue: 11
• Start Page: 2738
• End Page: 2746
• Grant/Funding Information: Data management through REDCap was supported by the National Institutes of Health grant UL1 TR000424.; This work was supported by an unrestricted grant from Immucor and by the US Centers for Disease Control and Prevention cooperative agreements DD14-1406, Characterizing the Complications Associated with Therapeutic Blood Transfusions for Hemoglobinopathies.
• Keywords: Life Sciences & Biomedicine; DISEASE; DONORS; ALLOIMMUNIZATION; COMPLICATIONS; PHENOTYPE; DNA ANALYSIS; Science & Technology; Hematology; MANAGEMENT; RISK
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology; Biology, Biostatistics

Abstract

BACKGROUND: Red blood cell (RBC) alloimmunization occurs at a high frequency in sickle cell anemia (SCA) despite serologic matching for Rh (C/c, E/e) and K antigens. RBC minor antigen genotyping allows for prediction of antigens and RH variants that may lead to alloimmunization. STUDY DESIGN AND METHODS: RBC antigen genotyping was performed on chronically transfused pediatric SCA patients, using PreciseType human erythrocyte antigen (HEA), RHCE, and RHD BeadChip arrays. All patients received C/c, E/e, and K serologically matched units (Category 1); patients with prior RBC antibodies were also matched for Fya, Jkb, and any antibodies (Category 2). The RBC genotypes of all leukoreduced (LR) units transfused over a 12-month period were determined by the prototype HEA-LR BeadChip assay. RESULTS: There were 2320 RBC units transfused to 90 patients in 1135 transfusion episodes. Thirty-five (38.9%) patients had homozygous or compound heterozygous RH variants. Seven new alloantibodies were detected, with alloantibody incidence of 0.706 in 100 units for Category 2 transfusions and 0.068 in 100 units for Category 1 (p = 0.02). Three patients on Category 2 transfusions formed new anti-Jsa and had a higher rate of exposure to Jsa than those who did not form anti-Jsa (20.4 vs. 8.33 exposures/100 units, p = 0.02). The most frequent mismatches were S (43.9%), Doa (43.9%), Fya (29.2%), M (28.4%), and Jkb (28.1%). CONCLUSIONS: Alloimmunization incidence was higher in those with prior RBC antibodies, suggesting that past immunologic responders are at higher risk for future alloimmunization and therefore may benefit from more extensive antigen matching beyond C/c, E/e, K, Fya, and Jkb.