IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels.
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.
Krampfl
K
K
Department of Neurology, Medical School Hannover, Germany.
Mohammadi
B
B
Buchwald
B
B
Jahn
K
K
Dengler
R
R
Toyka
K V
KV
Bufler
J
J
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018680:Cholinergic Antagonists / Q000276:immunology / Q000494:pharmacology; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018908:Muscle Weakness / Q000276:immunology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000276:immunology* / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000276:immunology*
D018680:Cholinergic Antagonists; D007074:Immunoglobulin G; D011978:Receptors, Nicotinic