Lambert-Eaton myasthenic syndrome: immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity.
We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (SCLC) on voltage-gated (K+-stimulated) 45Ca2+ flux in cell lines derived from a human SCLC (MAR10) and from a rat pheochromocytoma (PC12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2+ flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/10(6) cells; p less than 0.001) or non-SCLC-LEMS IgG (0.35 nmol/10(6) cells; p less than 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/10(6) cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC-associated LEMS.
Lang
B
B
Department of Neurological Science, Royal Free Hospital School of Medicine, Hampstead, London, UK.
Vincent
A
A
Murray
N M
NM
Newsom-Davis
J
J
D000200:Action Potentials; D000328:Adult; D000368:Aged; D000818:Animals; D015220:Calcium Channels / Q000276:immunology* / Q000502:physiology; D018288:Carcinoma, Small Cell / Q000150:complications / Q000276:immunology*; D002460:Cell Line; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology*; D007142:Immunoglobulin gamma-Chains / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009468:Neuromuscular Diseases / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology* / Q000502:physiology
D015220:Calcium Channels; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains