Serum autoantibodies found by radioimmunoassay in 27 of 52 patients with the Lambert-Eaton myasthenic syndrome (LES) bound specifically to a soluble ω-conotoxin binding component of a voltage-gated Ca2+ channel (VGCC) complex extracted from small cell lung carcinoma (SCC). These antibodies were not found in 43 control patients with other neurologic diseases, including myasthenia gravis, peripheral neuropathies, and amyotrophic lateral sclerosis, or in 9 patients with endocrine autoimmunity, but they were found in 2 of 21 control patients with SCC without a history of LES, 1 of whom had severe autonomic neuropathy. Seropositivity was more frequent in patients with LES who had evidence of a primary lung cancer (76%) than in those with other neoplasms or without evidence of cancer (30%). Antigens extracted from SCC tumor lines derived from patients with and without LES and from a human neuroblastoma line yielded results that were highly correlated. A control extract of colonic carcinoma (derived from a patient with LES) yielded negative results. The data implicate a tumor-associated VGCC as the autoimmunizing stimulus in a subset of patients with LES and provide the first direct evidence that the VGCC complex in SCC is a target for some LES antibodies. The serologic test described should be a useful aid in diagnosing LES.
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