Smith R G, Hamilton S, Hofmann F, Schneider T, Nastainczyk W, Birnbaumer L, Stefani E, Appel S H
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
N Engl J Med. 1992 Dec 10;327(24):1721-8. doi: 10.1056/NEJM199212103272405.
Sporadic amyotrophic lateral sclerosis is a chronic, progressive degenerative disease of the motor neurons of the spinal cord and motor cortex. The cause is unknown. Recent electrophysiologic studies in animals indicate that immunoglobulins from patients with this disease alter presynaptic voltage-dependent calcium currents and calcium-dependent release of neurotransmitters. To determine whether similar interactions might be identified biochemically, we used an enzyme-linked immunosorbent assay (ELISA) to detect the reaction of serum IgG with purified complexes of L-type voltage-gated calcium channels from rabbit skeletal muscle. The results from patients with amyotrophic lateral sclerosis were compared with those obtained from patients with other types of motor neuron disease, patients with autoimmune and non-autoimmune neurologic diseases, and normal subjects.
Serum samples from 36 of 48 patients with sporadic amyotrophic lateral sclerosis (75 percent) contained IgG that reacted with L-type calcium-channel protein, and serum reactivity on ELISA correlated with the rate of disease progression (Spearman rank-correlation coefficient, 0.62). Reactive serum was present in only 1 of 25 normal subjects and 1 of 35 control patients with no motor neuron disease. Antibodies to L-type voltage-gated calcium channels were identified in 6 of 9 patients with Lambert-Eaton syndrome, and in 3 of 15 patients with Guillain-Barré syndrome.
Antibodies to L-type voltage-gated calcium channels are present in the serum of patients with amyotrophic lateral sclerosis, and antibody titers correlate with the rate of disease progression. Together with previous data, these results suggest a role for autoimmune mechanisms in the pathogenesis of sporadic amyotrophic lateral sclerosis.
散发性肌萎缩侧索硬化症是一种脊髓和运动皮质运动神经元的慢性、进行性退行性疾病。病因不明。最近对动物的电生理研究表明，患有这种疾病的患者的免疫球蛋白会改变突触前电压依赖性钙电流以及神经递质的钙依赖性释放。为了确定是否可以通过生化方法识别类似的相互作用，我们使用酶联免疫吸附测定（ELISA）来检测血清IgG与兔骨骼肌L型电压门控钙通道纯化复合物的反应。将肌萎缩侧索硬化症患者的结果与其他类型运动神经元疾病患者、自身免疫性和非自身免疫性神经疾病患者以及正常受试者的结果进行比较。
48例散发性肌萎缩侧索硬化症患者中有36例（75%）的血清样本中含有与L型钙通道蛋白发生反应的IgG，ELISA上的血清反应性与疾病进展速度相关（Spearman等级相关系数为0.62）。25名正常受试者中只有1例以及35名无运动神经元疾病的对照患者中有1例出现反应性血清。在9例兰伯特-伊顿综合征患者中有6例以及15例吉兰-巴雷综合征患者中有3例检测到抗L型电压门控钙通道抗体。
肌萎缩侧索硬化症患者血清中存在抗L型电压门控钙通道抗体，抗体滴度与疾病进展速度相关。结合先前的数据，这些结果提示自身免疫机制在散发性肌萎缩侧索硬化症发病机制中起作用。
