Although the presence of "natural" antibodies capable of recognising foreign antigens could plausibly explain the role of IVIg in IgG replacement therapy, the precise mechanism of action by which IVIg exerts its immunomodulatory effects is not clearly understood. In inflammatory neuropathies there are several proposed pathophysiological mechanisms and a detailed review of these is beyond the scope of this article and has been dealt with elsewhere [25, 65, 67]. Pathological studies of nerve biopsies in CIDP and GBS reveal lymphocytic and macrophagic infiltrates in the endoneurium with deposits of IgM and complement components. The role of B-cells is clearly established in GBS where anti-ganglioside antibodies and complement activation have been demonstrated . Lymphocytic infiltrates are predominantly T-cells recruited by chemokines and endothelial cell adhesion molecules. T-cells secrete matrix metalloproteases which break down endoneurial proteins. Macrophages are the predominant antigen presenting cells as demonstrated by increased expression of NFκB and the inflammatory cytokines, IL-6 and IL-1β. All these mechanisms are potentially modulated by IVIg and will be discussed in detail below. Paradoxically, plasma exchange which works theoretically opposite to IVIg by removing IgG from the body, seem to work in similar clinical situations.
Jacob S, Rajabally YA. Current Proposed Mechanisms of Action of Intravenous Immunoglobulins in Inflammatory Neuropathies. Current Neuropharmacology. 2009;7(4):337-342. doi:10.2174/157015909790031166