Selected IgG rapidly induces Lambert-Eaton myasthenic syndrome in mice: complement independence and EMG abnormalities.
Antibodies in individual patients with the Lambert-Eaton myasthenic syndrome (LES) differ in their reactivity with mouse motor nerve terminals. Of 26 LES patients' sera injected a single time into mice, 3 caused a highly significant reduction in stimulus-dependent quantal release (m) of acetylcholine (ACh) (to 6, 33, and 42 quanta per impulse at 1 Hz, respectively; mean for 10 control sera, 100 quanta at 1 Hz). The most potent serum (LES-A) was fully effective in mice deficient in complement component C5 and in mice depleted of complement components C3----C9 by cobra venom factor. A single i.v. injection of serum reduced m in direct proportion to log dose. Responses to K+ depolarization and increasing concentrations of Ca2+ were like those observed in human LES. With LES-A serum, or its IgG, m was reduced near maximally in 1 day and plateaued in 3-4 days. Recovery began after day 8; m was in the normal range by day 20-30. Electromyographic (EMG) abnormalities were not seen until m fell below 40 quanta per impulse at 1 Hz. Below 10 quanta, clinical signs of weakness appeared, and the EMG abnormalities were those classically associated with LES: a marked reduction of compound muscle action potential to a single nerve stimulus in rested muscle, a further decrement during stimulation at slow rates, but marked facilitation during rapid repetitive stimulation.
Lambert
E H
EH
Department of Neurology, University of Minnesota, Minneapolis 55455.
Lennon
V A
VA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology; D004576:Electromyography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology*; D007267:Injections; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology* / Q000503:physiopathology; D009474:Neurons / Q000276:immunology; D011188:Potassium / Q000502:physiology
D007074:Immunoglobulin G; D003165:Complement System Proteins; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium