title: Immune modulation and lack of alloimmunization following transfusion with pathogen-reduced platelets in mice.
abstract: BACKGROUND
  Transfusion of allogeneic blood products can lead to alloimmunization, impacting success of subsequent transfusions and solid organ transplants. Pathogen reduction using riboflavin and ultraviolet B (UVB) light has been shown to eliminate the immunogenicity of white blood cells (WBCs) in vitro through down regulation of surface adhesion molecules, effectively blocking cell-cell conjugation and direct presentation. We sought to determine if this loss of immunogenicity is extended in vivo where indirect presentation of allogeneic antigens can occur.
  
  
  METHODS
  BALB/cJ mice were transfused with either untreated or riboflavin and UVB-treated C57Bl/6J platelet-rich plasma (PRP) containing WBCs. Circulating alloantibody and allospecific splenocyte cytokine responses were measured.
  
  
  RESULTS
  Pathogen reduction of allogeneic WBC-enriched PRP using riboflavin and UVB light before transfusion prevented alloimmunization, with a loss of both alloantibody generation and priming of secondary cytokine responses ex vivo. When mice given treated transfusions were subsequently given untreated transfusions, they produced normal levels of alloantibodies but had reduced secondary cytokine responses ex vivo. This immune modulation was antigen specific and was dependent on the presence of WBCs in the treated product.
  
  
  CONCLUSIONS
  UVB plus riboflavin treatment of WBC-enriched PRP effectively blocks alloimmunization and modulates immune responses to subsequent exposures.
authors: Blood Systems Research Institute, San Francisco, California; Department of Laboratory Medicine, University of California, San Francisco, California; Terumo BCT Biotechnologies, Lakewood, Colorado; Department of Medicine, University of California, San Francisco, California.
authors: Rachael P
authors: RP
authors: Jackman
authors: Marcus O
authors: MO
authors: Muench
authors: John W
authors: JW
authors: Heitman
authors: Heather C
authors: HC
authors: Inglis
authors: Jacqueline P
authors: JP
authors: Law
authors: Susanne
authors: S
authors: Marschner
authors: Raymond P
authors: RP
authors: Goodrich
authors: Philip J
authors: PJ
authors: Norris
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007518:Isoantibodies / Q000097:blood; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017713:Platelet Transfusion; D012256:Riboflavin / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines; D007518:Isoantibodies; D007519:Isoantigens; D012256:Riboflavin