Lang B, Vincent A, Murray N M, Newsom-Davis J
Department of Neurological Science, Royal Free Hospital School of Medicine, Hampstead, London, UK.
Ann Neurol. 1989 Mar;25(3):265-71. doi: 10.1002/ana.410250310.
We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (SCLC) on voltage-gated (K+-stimulated) 45Ca2+ flux in cell lines derived from a human SCLC (MAR10) and from a rat pheochromocytoma (PC12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2+ flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/10(6) cells; p less than 0.001) or non-SCLC-LEMS IgG (0.35 nmol/10(6) cells; p less than 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/10(6) cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC-associated LEMS.
我们比较了从小细胞肺癌（SCLC）患者和非SCLC患者获得的兰伯特-伊顿肌无力综合征（LEMS）免疫球蛋白G（IgG）对源自人SCLC（MAR10）和大鼠嗜铬细胞瘤（PC12）的细胞系中电压门控（K +刺激）45Ca2 +通量的影响，并将这些影响与临床严重程度的肌电图指标相关联。对照IgG取自患有其他神经系统疾病的患者或健康个体。LEMS IgG对Ca2 +通量的抑制具有时间和剂量依赖性。与在对照IgG中生长的MAR10细胞（0.7 nmol/10(6)个细胞）相比，在SCLC-LEMS IgG（0.38 nmol/10(6)个细胞；p <0.001）或非SCLC-LEMS IgG（0.35 nmol/10(6)个细胞；p <0.001）中生长的MAR10细胞中，通量显著降低。在PC12细胞中也观察到类似的显著降低。LEMS患者静息复合肌肉动作电位幅度的降低与其IgG对MAR10细胞中Ca2 +通量的抑制呈正相关（r = 0.70；p = 0.007）。这些结果有力地支持了这样一种观点，即能够抑制SCLC细胞中Ca2 +通量的IgG自身抗体是SCLC相关LEMS中运动神经递质释放紊乱的原因。
