Lambert-Eaton myasthenic syndrome.
The Lambert-Eaton myasthenic syndrome is associated in about 65% of cases with small cell carcinoma, a tumour of neurosecretory origin. It is characterised physiologically by a decrease in the nerve evoked quantal release of acetylcholine, and in the resting non-quantal release ("molecular leakage"). The associations with autoimmune disease, with other autoantibodies, with HLA-B8, and with the IgG heavy chain marker Glm (2) are consistent with an autoimmune aetiology. Clinical and electromyographic responses to plasma exchange point to a humorally mediated disorder. This has been substantiated by passive transfer of the the main electrophysiological features of LEMS to mice by daily injections of LEMS IgG. Plasma was no more effective in inducing the electrophysiological changes than the IgG fraction. The decrease in quantal content appeared closely to follow the level of human IgG in the mouse serum and complement (C5) deficient mice were as susceptible as normal controls. The principal physiological abnormalities are both Ca2+ dependent processes, suggesting that a defect in Ca2+ transport may underlie the disorder. Preliminary studies of quantal content at low Ca2+ concentrations in mice injected with LEMS IgG suggest the functional loss of 40% of Ca2+ channels. Electron microscopic freeze fracture studies in such animals show, as in the human disease, a significant reduction in the number of active zone particles which are believed to represent Ca2+ channels. Thus it seems likely that the disorder of acetylcholine release is due to an IgG antibody directed to nerve terminal determinants that include the Ca2+ channels or structures closely related to them. In cancer-associated LEMS, the autoantibody response may initially be made to similar determinants on the tumour cell membrane, cross-reactivity of the antibody with nerve terminal determinants leading to the disorder of transmitter release.
Newsom-Davis
J
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D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000150:complications; D002196:Capillaries; D018288:Carcinoma, Small Cell / Q000150:complications; D003165:Complement System Proteins / Q000502:physiology; D005121:Extremities; D006801:Humans; D007125:Immunogenetics; D007074:Immunoglobulin G / Q000276:immunology; D008175:Lung Neoplasms / Q000150:complications; D008214:Lymphocytes / Q000145:classification; D009135:Muscular Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000503:physiopathology; D009435:Synaptic Transmission; D013577:Syndrome; D013951:Thymus Hormones / Q000276:immunology
D000906:Antibodies; D007074:Immunoglobulin G; D013951:Thymus Hormones; C014859:thymic humoral factor; D003165:Complement System Proteins