title: Alloimmunization to transfused HOD red blood cells is not increased in mice with sickle cell disease.
abstract: BACKGROUND
  Increased rates of red blood cell (RBC) alloimmunization in patients with sickle cell disease may be due to transfusion frequency, genetic predisposition, or immune dysregulation. To test the hypothesis that sickle cell pathophysiology influences RBC alloimmunization, we utilized two transgenic mouse models of sickle cell disease.
  
  
  METHODS
  Transgenic sickle mice, which express human α and β(S) globin, were transfused with fresh or 14-day-stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffy(b) ) antigen; some recipients were inflamed with poly(I : C) before transfusion. Anti-HOD alloantibody responses were subsequently measured by enzyme-linked immunosorbent assay and flow crossmatch; a cohort of recipients had posttransfusion serum cytokines measured by bead array.
  
  
  RESULTS
  Both Berkeley and Townes homozygous (SS) and heterozygous (AS) mice had similar rates and magnitude of anti-HOD RBC alloimmunization after fresh HOD RBC transfusion compared with control animals; under no tested condition did homozygous SS recipients make higher levels of alloantibodies than control animals. Unexpectedly, homozygous SS recipients had blunted cytokine responses and lower levels of anti-HOD alloantibodies after transfusion of 14-day stored RBCs, compared with control animals.
  
  
  CONCLUSIONS
  In sum, homozygous β(S) expression and the ensuing disease state are not alone sufficient to enhance RBC alloimmunization to transfused HOD RBCs in two distinct humanized murine models of sickle cell disease under the conditions examined. These data suggest that other factors may contribute to the high rates of RBC alloimmunization observed in humans with sickle cell disease.
authors.affiliation: Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Atlanta, GA 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: Jennifer R
authors.initials: JR
authors.lastname: Perry
authors.forename: Samit
authors.initials: S
authors.lastname: Ghosh
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Chappa
authors.forename: Olufolake
authors.initials: O
authors.lastname: Adisa
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Kean
authors.forename: Solomon F
authors.initials: SF
authors.lastname: Ofori-Acquah
authors.forename: David R
authors.initials: DR
authors.lastname: Archer
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007518:Isoantibodies; C421864:hen egg lysozyme; D009113:Muramidase