Polyclonal IgG therapy in neurologic and neuromuscular disease: mechanisms of action and insights from newer therapies.

Abstract

Plasma-derived polyclonal IgG (IVIG or SCIG) has become the mainstay of therapy for autoimmune peripheral neuropathies including Guillain-Barre Syndrome, Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP) and Multifocal Motor Neuropathy, as well as Myasthenia Gravis. Use in these diseases exceeds that for all immune deficiencies combined. Laboratory and animal studies suggest many diverse mechanisms of action of IgG on cellular and humoral immunity. However, the spectrum of immune-mediated diseases in which IgG is efficacious is largely limited to conditions mediated by autoantibodies and/or complement. Careful analysis of clinical results indicates that only a few mechanisms are physiologically relevant: anti-idiotype neutralization, accelerated catabolism of IgG autoantibodies, and blockade of complement activation and deposition. These MOAs likely operate simultaneously and may contribute synergistically to the overall efficacy of IgG. Importantly, IgG does not act as a disease modifying drug, and repeat dosing at regular intervals is necessary in chronic diseases. This review seeks to provide a firm basis for understanding the mechanisms of action in vivo, and to provide benchmarks for understanding the effects and uses of new agents that have been recently approved and/or are under development.