Immunoglobulin G from patients with chronic inflammatory demyelinating polyneuropathy (CIDP) affects presynaptic transmitter release and calcium influx

Chronic inflammatory demyelinating polyneuropathy (CIDP), considered the peripheral counterpart of multiple sclerosis, is an acquired peripheral nerve disorder of presumed autoimmune aetiology emerging from cell-mediated and humoral immune responses directed against incompletely characterized peripheral nerve antigens. To test for a possible role of humoral factors in the pathogenesis of CIDP, we investigated the effects of purified immunoglobulin G (IgG) from ten patients with typical CIDP on neuromuscular transmission by a perfused macro-patch-clamp-electrode in mouse hemidiaphragms and examined the influence of these IgGs on calcium influx in cultured principal neurons by calcium imaging. Compared to control-IgGs, application of CIDP-IgGs to the nerve terminal led to a significantly reduced quantal release. The extent and mode of this presynaptic effect differed between patients. Depolarization-induced calcium influx in cultured neurons was significantly reduced after application of CIDP-IgG of four patients. Coincubation of CIDP-IgGs with therapeutical intravenous Immunoglobulins (IVIg) completly neutralized these blocking effects. These findings provide evidence that muscle weakness in CIDP-patients may be caused in part by circulating antibodies.