IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels

Abstract

In Guillain-Barré syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.