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Lambert‐eaton myasthenic syndrome: Immunoglobulin G inhibition of Ca 2+ flux in tumor cells correlates with disease severity
Author(s) -
Lang B.,
Vincent A.,
Murray N. M. F.,
NewsomDavis J.
Publication year - 1989
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410250310
Subject(s) - antibody , lambert eaton myasthenic syndrome , disease , medicine , flux (metallurgy) , immunoglobulin g , immunology , pathology , chemistry , organic chemistry
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) 45 Ca 2+ 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 Ca 2+ 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 < 0.001) or non‐SCLC‐LEMS IgG (0.35 nmol/10 6 cells; p < 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 Ca 2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca 2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC‐associated LEMS.