Calcium Channel Autoantibodies in Myasthenic Syndrome and Small Cell Lung Cancer

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Abstract
Lambert-Eaton myasthenic syndrome (LEMS) is one of the neurologic paraneoplastic syndromes often found in patients with lung cancer. It is characterized by a generalized deficit of neurotransmitter release. Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS. LEMS is an autoimmune disease, and autoantibodies that interfere with neurotransmitter release by binding to presynaptic voltage-operated calcium channels (VOCCs) have been found in sera of patients with LEMS. Both human neuronal and SCLC cell lines express omega-conotoxin-sensitive VOCCs, and autoantibodies from patients affected by LEMS can precipitate these channels. We have now screened a large population of patients and control subjects in order to define the specificity and sensitivity of the anti-VOCC antibody assay. We have tested sera from 52 patients with LEMS with and without SCLC; 32 sera from patients with SCLC without LEMS, 31 from patients with non-SCLC, 34 from patients with inflammatory lung diseases, 17 from patients with other neurologic disorders, and 48 from healthy control subjects. We have found that a positive result with this radioimmunoassay is highly specific for LEMS, with or without SCLC, when the antibody titer is higher than 14.21 pM. Anti-VOCC antibodies have also been found in about 40% of patients with SCLC without LEMS, but they were absent in all the other populations tested. We can conclude that this serologic assay is a very useful aid in the diagnosis of LEMS, and it might be useful also for the early diagnosis of SCLC.