Autoimmune autonomic ganglionopathy - IgG effects on ganglionic acetylcholine receptor current
Autoimmune autonomic ganglionopathy - IgG effects on ganglionic acetylcholine receptor current
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DOI：
10.1212/01.wnl.0000263185.30294.61
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发表时间：
2007-05-29
期刊：
影响因子：
9.9
通讯作者：
Vernino, S.
中科院分区：
文献类型：
--
作者：
Wang, Z.;Low, P. A.;Vernino, S.
背景：自身免疫性自主神经节病（AAG）是一种获得性免疫介导的弥漫性自主神经衰竭。许多患者的血清抗体与神经节乙酰胆碱受体（AChR）结合，介导自主神经节的快速突触传递。先前的临床研究和动物模型观察表明，AAG 是一种抗体介导的神经系统疾病。方法：使用全细胞膜片钳技术，我们记录了培养的人 IMR-32 细胞中的神经节 AChR 电流，并检查了来自 AAG 患者的 IgG 浴应用的效果。结果：7 名 AAG 患者的 IgG 均导致全细胞神经节 AChR 电流进行性下降，而对照受试者的 IgG 则没有影响。低温时该作用消失。除非同时添加二抗，否则 Fab 抗体片段没有作用。一名患者的 IgG 还可以更直接地减少神经节 AChR 电流。结论：抗体介导的神经节乙酰胆碱受体（AChR）电流抑制的特征与膜AChR的调节和阻断一致，类似于肌肉AChR抗体在重症肌无力中的作用。我们的观察表明，自身免疫性自主神经节病 (AAG) 患者体内的抗体会引起神经节 AChR 功能的生理变化，并证实 AAG 是一种抗体介导的疾病。
Background: Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (AChRs) that mediate fast synaptic transmission in autonomic ganglia. Previous clinical studies and observations in animal models suggest that AAG is an antibody-mediated neurologic disorder. Methods: Using whole-cell patch clamp techniques, we recorded ganglionic AChR currents in cultured human IMR-32 cells and examined the effects of bath application of IgG derived from patients with AAG. Results: IgG from seven patients with AAG all produced a progressive decline in whole-cell ganglionic AChR current, whereas IgG from control subjects had no effect. The effect was abolished at low temperature. Fab antibody fragments had no effect unless a secondary antibody was added concurrently. IgG from one patient also produced a more immediate reduction of ganglionic AChR current. Conclusions: The characteristics of antibody-mediated inhibition of ganglionic acetylcholine receptor ( AChR) current are consistent with modulation and blocking of the membrane AChR, analogous to the effects of muscle AChR antibodies in myasthenia gravis. Our observations demonstrate that antibodies in patients with autoimmune autonomic ganglionopathy ( AAG) cause physiologic changes in ganglionic AChR function and confirm that AAG is an antibody-mediated disorder.