The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?
Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.
Crow
Andrew R
AR
Department of Laboratory Medicine, St. Michael's Hospital, Ontario, Canada.
Lazarus
Alan H
AH
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D018029:Rho(D) Immune Globulin / Q000276:immunology / Q000494:pharmacology*
C499173:FCGR2B protein, human; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D018029:Rho(D) Immune Globulin