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Heterogeneity of calcium channel autoantibodies detected using a small-cell lung cancer line derived from a Lambert-Eaton myasthenic syndrome patient

Neurosciences Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

We investigated the heterogeneity of anti-voltage-gated calcium channel (VGCC) antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) using a small-cell lung carcinoma line (MB) derived from an LEMS patient. Four of 13 LEMS patients had raised titers of anti-¹²⁵I--conotoxin-labeled (N-type) VGCCs, measured by radioimmunoassay using line MB as the source of antigen. Antagonists for L-type (nitrendipine and nifedipine) and retype (-conotoxin) VGCCs inhibited K⁺-stimulated (voltage-dependent) Ca²⁺ flux into this line-by 22% for L-type and 2% for N-type at maximum concentration. Inhibition by the LEMS IgGs, by contrast, ranged from 46 to 78% at a concentration of 2 mg/ml. These differing effects on Ca²⁺ flux inhibition by LEMS IgGs on the one hand and by L- and N-type channel antagonists on the other, taken together with the observation that many of the sera failed to react with -conotoxin-labeled (N-type) channels in the immunoprecipitation assay, suggest that in many LEMS patients the autoantibodies target other VGCC subtypes besides L- or N-types, and that these are important in inducing the myasthenic disorder.

Address correspondence and reprint requests to Dr. B. Lang, Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford 0X3 9DU, UK.

Supported by the Medical Research Council, the A.J. Florey Fund (K.L.), and the Sir Jules Thorn Charitable Trust (I.J.).

Received April 7, 1993. Accepted for publication in final form July 26, 1993.

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