[Autoantibody against the presynaptic P/Q-type voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome].
[Autoantibody against the presynaptic P/Q-type voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome].
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兰伯特-伊顿肌无力综合征中突触前 P/Q 型电压门控钙通道的自身抗体。
DOI：
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
H. Matsuo
中科院分区：
文献类型：
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作者：
W. Sakai;S. Nakane;H. Matsuo
在20世纪70年代，针对肌肉乙酰胆碱受体（AChR）的抗体被认为是重症肌无力的原因。从那时起，其他与自身抗体相关的神经系统疾病已经被确定，每种疾病都与针对配体或电压门控离子通道的抗体相关。在Lambert-Eaton肌无力综合征（LEMS）患者中检测到针对P/Q型电压门控钙通道（VGCC）的自身抗体。这些抗体干扰乙酰胆碱从突触前膜的钙依赖性释放。LEMS是一种影响神经肌肉接头的自身免疫性疾病，其特征在于近端肌无力、腱反射减少和自主神经功能障碍。电生理检查显示小幅度复合肌肉动作电位和快速重复神经刺激的增量。50%至60%的LEMS患者存在肿瘤，主要是小细胞肺癌（SCLC），作为副肿瘤综合征。SCLC是一种神经内分泌肿瘤，其表达神经元VGCC。部分患者出现小脑性共济失调，常伴有小细胞肺癌。这些患者倾向于显示比无共济失调的LEMS患者更高的VGCC抗体滴度。通过发现静息时复合肌肉动作电位振幅降低，重复神经刺激和使用放射免疫沉淀测定进行抗体检测时显示增量大于100%，可以确认诊断。治疗选择通常分为抗肿瘤、免疫调节、免疫抑制和对症治疗。在SCLC病例中，有效的肿瘤治疗可以改善LEMS。血浆置换术和静脉注射大剂量免疫球蛋白的效果较短。泼尼松，单独或与免疫抑制剂联合使用，可以实现长期控制的障碍。
Antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis in the 1970s'. Since then, other neurological disorders associated with autoantibodies have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs) are detected in patients with Lambert-Eaton myasthenic syndrome (LEMS). These antibodies interfere with the calcium-dependent release of acetylcholine from the presynaptic membrane. LEMS is an autoimmune disorder affecting the neuromuscular junction, and is characterized by proximal muscle weakness, reduction of tendon reflex, and autonomic dysfunction. Electrophysiological examinations show small-amplitude compound muscle action potentials and increments on rapid repetitive nerve stimulation. Fifty to sixty percent of LEMS patients present with tumors, mostly small cell lung carcinoma (SCLC), as a paraneoplastic syndrome. SCLC is a neuroendocrine tumor, which expresses neuronal VGCCs. Some patients present cerebellar ataxia, which is always accompanied by SCLC. These patients tend to show higher titers of VGCC antibodies than that by LEMS patients with no ataxia. The diagnosis can be confirmed by finding reduced compound muscle action potential amplitudes at rest that shows increments greater than 100% with repetitive nerve stimulation and antibody detection by using radioimmunoprecipitation assays. The treatment options are generally categorized as anti-tumor, immunomodulating, immunosuppressing, and symptomatic treatments. In cases with SCLC, effective treatment against the tumor can improve LEMS. Plasmapheresis and intravenous administration of high-dose immunoglobulins have a short effect. Prednisone, alone or in combination with immunosuppressants can achieve long-term control of the disorder.