Lambert‐eaton myasthenic syndrome: Immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity

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Abstract
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/106 cells; p < 0.001) or non‐SCLC‐LEMS IgG (0.35 nmol/106 cells; p < 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/106 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.