title: Storage of murine red blood cells enhances alloantibody responses to an erythroid-specific model antigen.
abstract: BACKGROUND
  Red blood cell (RBC) alloimmunization can be a serious complication of blood transfusion, but factors influencing the development of alloantibodies are only partially understood. Within FDA-approved time limits, RBCs are generally transfused without regard to length of storage. However, recent studies have raised concerns that RBCs stored for more than 14 days have altered biologic properties that may affect medical outcomes. To test the hypothesis that storage time alters RBC immunogenicity, we utilized a murine model of RBC storage and alloimmunization.
  
  
  METHODS
  Blood from transgenic HOD donor mice, which express a model antigen (hen egg lysozyme [HEL]) specifically on RBCs, was filter leukoreduced and stored for 14 days under conditions similar to those used for human RBCs. Fresh or 14-day-stored RBCs were transfused into wild-type recipients. The stability of the HOD antigen and posttransfusion RBC survival were analyzed by flow cytometry. RBC alloimmunization was monitored by measuring circulating anti-HEL immunoglobulin levels.
  
  
  RESULTS
  Transfusion of 14-day-stored, leukoreduced HOD RBCs resulted in 10- to 100-fold higher levels of anti-HEL alloantibodies as detected by enzyme-linked immunosorbent assay than transfusion of freshly collected, leukoreduced RBCs. RBC expression of the HOD antigen was stable during storage.
  
  
  CONCLUSIONS
  These findings demonstrate that HOD murine RBCs become more immunogenic with storage and generate the rationale for clinical trials to test if the same phenomenon is observed in humans. Length of storage of RBCs may represent a previously unappreciated variable in whether or not a transfusion recipient becomes alloimmunized.
authors.affiliation: Division of Pediatric Hematology/Oncology, AFLAC Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA. jeanne.hendrickson@choa.org
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Hendrickson
authors.forename: Eldad A
authors.initials: EA
authors.lastname: Hod
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hillyer
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
mesh_terms: D000818:Animals; D001787:Blood Group Incompatibility / Q000235:genetics / Q000276:immunology*; D001793:Blood Preservation; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007519:Isoantigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D013997:Time Factors
chemical_list: D007518:Isoantibodies; D007519:Isoantigens