Purified IgG from seropositive and seronegative patients with mysasthenia gravis reversibly blocks currents through nicotinic acetylcholine receptor channels

Annals of Neurology
J BuflerC Franke

Abstract

The mechanism of block of nicotinic acetylcholine receptor (nAChR) channels by purified antibodies from patients with myasthenia gravis (MG) was investigated by using an ultrafast system for solution exchange at outside-out patches. IgG of MG patients and controls was purified by using protein A-Sepharose columns. Probes from 9 seropositive MG patients and 3 seronegative MG patients were tested. As a preparation, cultured mouse myotubes expressing the embryonic-type nAChR channels were used. Twenty-millisecond pulses of 1.0 mM ACh were applied repetitively to outside-out patches. Outside-out patches were preexposed with IgG in concentrations between 0.1 and 200 mg/L during application of ACh pulses. The peak current amplitude was reduced to values between 6% and 71% of control for the 9 seropositive and 3 seronegative MG patients. The block was concentration dependent and fully reversible after washout of antibodies. Incubation with IgG from different control patients did not reduce the peak current amplitude. In addition, our findings with purified IgG from seronegative MG patients support the idea of the immunopathogenesis of this disorder and may allow the development of a diagnostic test for seronegative MG patients.

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Citations

Mar 15, 2000·Muscle & Nerve·J M Lindstrom
Mar 1, 2002·Muscle & Nerve·Klaus KrampflJohannes Bufler
Feb 8, 2013·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Rumi SatoTadashi Miyatake
Dec 23, 1999·Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis·H MatsuoN Shibuya
Jun 3, 2008·Brain : a Journal of Neurology·Maria Isabel LeiteAngela Vincent
Jun 19, 2008·Brain : a Journal of Neurology·Jon Lindstrom
Oct 4, 2006·Neuron·Angela VincentKleopas A Kleopa
May 22, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Oliver Harschnitz
Jan 26, 2016·Nature Reviews. Neuroscience·Sarah J CrispAngela Vincent
Dec 11, 1999·Current Opinion in Neurology·A Vincent
Mar 14, 2020·Journal of Neurology, Neurosurgery, and Psychiatry·Hakan CetinAngela Vincent
Jul 5, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·P J Spring, J M Spies

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