New treatment strategies for systemic vasculitis: The role of intravenous immune globulin therapy

Intravenous immune globulin (IVIG) is now under evaluation for the treatment of patients with the forms of systemic vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA). Although IVIG may produce effects by a variety of mechanisms, including control of T-cell function, interference with cytokine action, and Fc receptor blockade, it is the regulation of autoantibody production by B cells, through idiotypic-anti-idiotypic reactions, that makes this treatment attractive for patients with systemic vasculitis. The author and others have shown the importance of ANCA idiotypic-anti-idiotypic reactions in vitro and demonstrated that these could be influenced by anti-idiotypic determinants present in IVIG. Thus F(ab')(2) fragments of IVIG could block ANCA binding to antigen, in a dose-dependent fashion. The degree of inhibition was variable, ranging up to 100% for the ANCA-containing sera of certain patients. Similar inhibitory activity could be found in the sera of patients in remission after treatment, as well as in occasional patients whose disease remitted spontaneously, without drugs being used. Thus, IVIG appears to be particularly valuable in the management of vasculitis in the elderly, the very young and for pregnant women, as well as for those at any age who are vulnerable to infection.