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Am J Hematol. 2015 Dec;90(12):1135-41. doi: 10.1002/ajh.24188. Epub 2015 Oct 6.

Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion.

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Division of Hematology, Children's National Health System, Washington, District of Columbia.
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Emory University, Atlanta, Georgia.
Center for Transfusion and Cellular Therapy, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.
Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Department of Pediatrics, University of Washington, and the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Laboratory Medicine, Yale University, New Haven, Connecticut.
Department of Pediatrics, Yale University, New Haven, Connecticut.


Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non-responders), a cross-sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non-alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non-alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization.

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