Lennon V A, Kryzer T J, Griesmann G E, O'Suilleabhain P E, Windebank A J, Woppmann A, Miljanich G P, Lambert E H
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
N Engl J Med. 1995 Jun 1;332(22):1467-74. doi: 10.1056/NEJM199506013322203.
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.
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.
P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small-cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with 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.
The high frequency of P/Q-type calcium-channel antibodies found in patients with Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.
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兰伯特-伊顿综合征中的自身免疫反应。但具体负责的钙通道亚型尚不清楚。
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去极化依赖性钙-45内流的影响。检测了患有各种疾病患者的血清样本与从癌细胞膜和小脑膜中溶解的P/Q型通道以及大脑皮质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45Ca内流的最有效抑制剂。在所有32例诊断为癌症的兰伯特-伊顿综合征患者以及33例无癌症的兰伯特-伊顿综合征患者中的91%的血清中发现了抗P/Q型钙通道抗体。在65例兰伯特-伊顿综合征患者中的49%发现了抗N型钙通道抗体。在70例患有肺、卵巢或乳腺癌的副肿瘤性脑脊髓神经病并发症的患者中的54%、90例患有癌症但无明显神经并发症的患者中的24%、78例散发性肌萎缩侧索硬化患者中的23%以及69例重症肌无力、癫痫或硬皮病患者中的不到3%发现了较低滴度的抗P/Q型和抗N型钙通道抗体。
兰伯特-伊顿综合征患者中发现的P/Q型钙通道抗体的高频率表明这种特异性抗体在该疾病的突触前病理生理过程中起作用。
