title: Monoclonal antibody-mediated inhibition of the human HLA alloimmune response to platelet transfusion is antigen specific and independent of Fcgamma receptor-mediated immune suppression.
abstract: Presensitization of donor platelets with allo-specific immunoglobulin (Ig)G results in a diminished immune response against subsequent transfusions of platelets. To understand better the mechanism of how alloantibody presensitization results in a decreased alloimmune response, we have used murine monoclonal antibodies directed to polymorphic and non-polymorphic regions of human leucocyte antigen (HLA) as well as platelet-specific molecules. Here, we demonstrated that presensitization with anti-human HLA class I antibodies, as well as beta2-microglobulin-specific antibody, protected against alloantibody production to five subsequent untreated platelet challenges. Use of complement fixing, non-fixing or F(ab')2 fragments of HLA-specific antibody also resulted in complete inhibition of alloantibody production. This protection was not seen when the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32 (low-affinity IgG/Fcgamma receptor) or murine IgG and was thus independent of B-cell FcgammaRII-mediated immune suppression. The inhibition observed was independent of HLA alloantigenic specificity as antibodies directed at the beta2-microglobulin portion of HLA class I were as effective as antibodies against any of the HLA-alpha regions (either polymorphic or non-polymorphic) of class I. This work demonstrates that monoclonal antibody-mediated suppression of the human HLA alloimmune response to platelet transfusion is antigen specific and is independent of FcgammaRII-mediated immune regulation, complement fixing or HLA alloantigenic specificity.
authors.affiliation: Transfusion Medicine Research and the Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Crow
authors.forename: J
authors.initials: J
authors.lastname: Freedman
authors.forename: B
authors.initials: B
authors.lastname: Hannach
authors.forename: A H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D015551:Autoimmunity / Q000502:physiology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D017713:Platelet Transfusion; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D017452:Receptors, IgG