CALCIUM-CHANNEL ANTIBODIES IN THE LAMBERT-EATON SYNDROME AND OTHER PARANEOPLASTIC SYNDROMES
CALCIUM-CHANNEL ANTIBODIES IN THE LAMBERT-EATON SYNDROME AND OTHER PARANEOPLASTIC SYNDROMES
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DOI：
10.1056/nejm199506013322203
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发表时间：
1995-06-01
影响因子：
158.5
通讯作者：
LAMBERT, EH
中科院分区：
文献类型：
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作者：
LENNON, VA;KRYZER, TJ;LAMBERT, EH
背景小细胞肺癌中的电压门控钙通道可能引发副肿瘤性神经肌肉疾病Lambert-Eaton综合征的自身免疫负责的钙通道亚型是未知的。我们比较了L-型，N-型和P/Q-型神经元钙通道拮抗剂对培养的癌细胞中钙-45去极化依赖性内流的影响。检测了不同疾病患者的血清样品与肿瘤和小脑膜溶解的P/Q型通道和大脑皮层溶解的N型通道的反应性。P/Q型钙通道拮抗剂是培养的小细胞癌细胞系中去极化诱导的Ca-45内流的最有效的抑制剂。在所有32名患有Lambert-Eaton综合征并被诊断为癌症的患者的血清中发现了抗P/Q型钙通道抗体，在33名患有Lambert-Eaton综合征但没有癌症的患者中，有91%的患者的血清中发现了抗P/Q型钙通道抗体。在65名Lambert-Eaton综合征患者中，有49%的人发现了抗N型钙通道抗体。在70例肺癌、卵巢癌或乳腺癌的副肿瘤性脑脊髓神经病并发症患者中，54%的患者发现抗P/Q型和抗N型钙通道抗体滴度较低，在90例癌症但无明显神经系统并发症的患者中，24%的患者发现抗P/Q型和抗N型钙通道抗体滴度较低，在78例散发性肌萎缩侧索硬化症患者中，23%的患者发现抗P/Q型和抗N型钙通道抗体滴度较低，而在69例重症肌无力、癫痫或硬皮病患者中，低于3%。在Lambert-Eaton综合征患者中发现的P/Q型钙通道抗体的高频率意味着这种特异性的抗体在这种疾病的突触前病理生理学中起作用。
Background. Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known.Methods. We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity 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 depolarization-induced Ca-45 influx in cultured small-cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert-Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma.Conclusions. The high frequency of P/Q-type calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.