Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal
Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal
复制标题
DOI：
10.1093/brain/124.5.893
复制
发表时间：
2001-05-01
期刊：
影响因子：
14.5
通讯作者：
Willison, HJ
中科院分区：
文献类型：
--
作者：
O'Hanlon, GM;Plomp, JJ;Willison, HJ
Miller-Fisher 综合征是一种自身免疫性神经病，其特征为共济失调、反射消失和眼肌麻痹，并且在大多数情况下存在高滴度的抗 GQ1b 神经节苷脂抗体。在离体模型中，人和小鼠抗 GQ1b 抗体先前已被证明可在小鼠运动终板上诱导补体依赖性 α -河豚毒素样作用，即它们会导致乙酰胆碱的大量量子释放并最终阻断神经肌肉传递，使用免疫荧光显微镜和图像分析，我们在这里表明，这种电生理效应的后期阶段在时间上与重神经丝（200 kDa）和III型β-微管蛋白免疫染色的损失以及神经末梢的结构破坏同时发生，如电子显微镜所证明的那样。从超微结构上看，轴突末端杂乱无章，囊泡耗尽，并被雪旺细胞帽的浸润过程细分。这些发现提供了明确的病理证据，支持抗神经节苷脂抗体在介导神经末梢损伤中的作用，并进一步推进了这一观点，即该位点可能作为某些人类神经病的重要靶点。
Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies, In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent alpha -latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission, Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III beta -tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells, These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.