Mechanism of IVIg Therapy In Antibody-Medicated Autoimmune Disease

IntraVenous administration of high doses of IgG pooled from the Plasma of healthy donors has benefited patients with a variety of Auto Immune Disorders. Although its mechanism of action is not known, Immune Globulin is acknowledged as an effective and beneficial alternative to Plasmapheresis. For treating diseases that are thought to be mediated by pathogenic Auto Antibodies or Immune complexes. It is used increasingly to treat Neurologic Diseases such as inflammatory DeMyelinating Neuropathies, Multifocal Motor Neuropathy, Inflammatory Myopathies, Myasthenia Gravis, and the Lambert-Eaton Syndrome. The efficacy of Immune Globulin therapy has formally been proved only for the Guillain-Barre Syndrome and chronic inflammatory DeMyelinating PolyNeuropathies. However, accounts of new applications continue to arise, like the use of this therapy for Rasmussen's Encephalitis. Numerous mechanisms have been suggested to explain the beneficial action of high doses of normal IgG in AntiBody-mediated disorders, but none satisfactorily explained all clinical situations.

Therapeutic concentrations of IgG have been shown to block Fc receptors on Phagocytes and on Cellular Effectors of AntiBody-dependent cytotoxicity. These receptors bind to the stem of the Y-shaped IgG molecule. The Fc region mediates the effector properties of the molecule but not its Immunologic specificity, which counts on the two extended arms of the Y. Blockade of Fc receptors is a reasonable mechanism for improving the Cytopenia of Idiopathic Thrombocytopenic Purpura and the destruction of Myelin in the Guillain-Barre Syndrome. It is unlikely to explain how an elevation of Serum IgG brought about by treatment with Immune Globulin relieves the chronic blockade of Synaptic transmission in Myasthenia Gravis, which is mediated by pathogenic IgG. Various ImmunoModulatory properties have been assigned to pooled preparations of IgG, including regulatory properties of AntiIdiotypic AntiBodies and effects on Cytokine synthesis and on receptors for Cytokines.

Note: There is no compelling evidence that any of these postulated mechanisms account for the therapeutic benefits.

Medicine has its office, it does its share and does it well; but without hope back of it, its forces are crippled and only the physician's verdict can create that hope when the facts refuse to create it.

- Mark Twain -