Transfusion‐induced alloimmunization and platelet refractoriness in a mouse model: mechanisms and interventions. Issue 1 (24th September 2015)

• Record Type: Journal Article
• Authors: Waterman, Hayley R.; Kapp, Linda M.; Munday, Adam; Odem‐Davis, Katherine; Zimring, James C.
• Is Part Of: Transfusion. Volume 56:Issue 1(2016:Feb.)
• Page Start: 91
• Page End: 100
• Publication Date: 2015-09-24
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.13270
• Languages: English
• ISSNs: 0041-1132

Abstract

Abstract : BACKGROUND: Platelet (PLT) transfusions can be an essential therapy for patients with thrombocytopenia to maintain hemostasis. However, some patients become alloimmunized to antigens on PLTs (typically HLA), which can prevent efficacy of PLT transfusion due to antibody‐mediated clearance. In extreme cases, patients with alloimmunization to multiple HLAs can become "refractory" to PLT transfusion, such that insufficient compatible PLT units can be found to meet transfusion needs. MATERIALS AND METHODS: An in vivo murine model of PLT‐induced alloimmunization was refined so as to include both transfusion with allogeneic leukoreduced PLTs and studies of posttransfusion PLT recoveries, allowing assessment of alloimmunization and refractoriness. Basic mechanisms of antibody‐mediated PLT clearance were investigated using recipients missing either the C3 complement gene or the common gamma chain for Fc receptors. In addition, the efficacy of using costimulatory blockade as a therapeutic intervention was assessed by testing CTLA4‐Ig administration before PLT transfusion. RESULTS: Fcγ receptors (but not complement C3) are required for alloantibody‐mediated PLT refractoriness. In addition, levels of anti‐MHC predict the extent of refractoriness in a given animal. Finally, costimulatory blockade as a therapeutic modality prevents transfusion‐induced PLT refractoriness. CONCLUSIONS: Together these findings introduce new experimental methods, basic mechanistic understanding, and a potential therapeutic intervention for alloimmunization to MHC‐based antigens on transfused PLTs.