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IgG from patients with Guillain–Barré syndrome interact with nicotinic acetylcholine receptor channels
Author(s) -
Krampfl K.,
Mohammadi B.,
Buchwald B.,
Jahn K.,
Dengler R.,
Toyka K.V.,
Bufler J.
Publication year - 2003
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.10349
Subject(s) - myasthenia gravis , acetylcholine receptor , neuromuscular transmission , nicotinic acetylcholine receptor , neuromuscular junction , nicotinic agonist , acetylcholine , chemistry , receptor , immunology , medicine , biology , neuroscience
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. Muscle Nerve 27:435–441, 2003