CALCIUM-CHANNEL ANTIBODIES IN THE LAMBERT-EATON SYNDROME AND OTHER PARANEOPLASTIC SYNDROMES

Background. Voltage-gated calcium channels in small-cell lung carcinom as may initiate autoimmunity in the paraneoplastic neuromuscular disor der Lambert-Eaton syndrome. The calcium-channel subtype that is respon sible is not known. Methods. We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal calcium channels on the depolar ization-dependent influx of calcium-45 in cultured carcinoma cells. Se rum samples from patients with various disorders were tested for react ivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results. P/Q-type calcium-channel antagonists were the most potent inhibitors of depola rization-induced Ca-45 influx in cultured small-cell carcinoma cell li nes. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of ca ncer and in 91 percent of the 33 patients with the Lambert-Eaton syndr ome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lowe r titers of anti-P/Q-type and anti-N-type calcium-channel antibodies w ere found in 54 percent of 70 patients with a paraneoplastic encephalo myeloneuropathic complication of lung, ovarian, or breast carcinoma, 2 4 percent of 90 patients with cancer but no evident neurologic complic ations, 23 percent of 78 patients with sporadic amyotrophic lateral sc lerosis, and less than 3 percent of 69 patients with myasthenia gravis , epilepsy, or scleroderma. Conclusions. The high frequency of P/Q-typ e calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in th e presynaptic pathophysiology of this disorder.