Mechanisms of action of intravenous immunoglobulin in the treatment of immune thrombocytopenia.
Intravenous immunoglobulin (IVIG) is currently used to treat a multitude of autoimmune disorders including immune thrombocytopenic purpura (ITP), yet the mechanism of action of IVIG remains unresolved. Using a murine model of ITP in which IVIG functions therapeutically, our laboratory has addressed such theories as blockade/inhibition of the mononuclear phagocytic system, cytokine regulation, and neutralization of pathogenic autoantibodies mediated by anti-idiotypic antibodies, and these findings will be discussed herein. We have also demonstrated that soluble immune complexes can completely recapitulate the therapeutic effects of IVIG in ITP, and recent work from us has identified activating Fcgamma receptors on CD11c+ dendritic cells as the relevant molecular target of IVIG in the acute resolution of murine immune thrombocytopenia. This and other work to devise antibody-based IVIG alternative therapies will also be addressed.
Crow
Andrew R
AR
The Canadian Blood Services, Department of Laboratory Medicine, St Michael's Hospital and University of Toronto, Ontario, Canada.
Song
Seng
S
Siragam
Vinayakumar
V
Lazarus
Alan H
AH
D000818:Animals; D000936:Antigen-Antibody Complex / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D051379:Mice; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000628:therapy*; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000276:immunology
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; C499172:Fcgr2b protein, mouse; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG