Neuroimmunology Unit, Department of Pathophysiology, Faculty of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Goudi, Athens 11527, Greece.
Nat Rev Neurol. 2015 Mar;11(3):143-56. doi: 10.1038/nrneurol.2014.260. Epub 2015 Jan 27.
Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.
越来越多的证据表明，自身抗体有助于周围神经系统和中枢神经系统脱髓鞘的发病机制。在急性或慢性炎性脱髓鞘性多发性神经病中，血浆置换或静脉注射免疫球蛋白治疗后电生理阻滞的快速逆转，更可能是由于清除或中和了一种损害跳跃传导的抗体，而不是由于髓鞘再生。尽管多达 30%的急性或慢性炎性脱髓鞘性多发性神经病患者存在自身抗体，但在不超过 13%的病例中已确定了特定的抗原。迄今为止，在Ranvier 结中鉴定出的自身抗原包括神经束蛋白 186、神经胶质蛋白和可能在节段域中的膜突蛋白，以及在连接蛋白域中的接触蛋白-1、Caspr1 和神经束蛋白 155。在一些多发性硬化症患者中，连接蛋白-1 聚糖酶和连接蛋白-2 触发体液反应。这篇综述探讨了 Ranvier 结的分子解剖结构，重点关注具有细胞外结构域的蛋白质，这些蛋白质可能作为抗原。还讨论了节段特异性抗体反应的临床意义，并强调了识别针对结蛋白的抗体的最佳方法。还讨论了这些抗体作为二次、加重疾病的反应的作用，或者作为定义结处脱髓鞘或轴突变性、确定疾病亚型或决定对治疗反应的主要效应机制的作用。
