Demyelination diseases involving the central and peripheral nervous systems are etiologically heterogeneous with both cell-mediated and humoral immunities playing pathogenic roles. Recently, autoantibodies against nodal and paranodal proteins, such as neurofascin186 (NF186), neurofascin155 (NF155), contactin-1 (CNTN1), contactin-associated protein 1 (CASPR1) and gliomedin, have been discovered in not only chronic demyelinating conditions, such as multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy, but also in acute demyelinating conditions, such as Guillain-Barré syndrome. Only a minority of these patients harbor anti-nodal/paranodal protein antibodies; however, these autoantibodies, especially IgG4 subclass autoantibodies to paranodal proteins, are associated with unique features and these conditions are collectively termed nodopathy or paranodopathy. Establishing a concept of IgG4-related nodopathy/paranodopathy contributes to diagnosis and treatment strategy because IgG4 autoantibody-related neurological diseases are often refractory to conventional immunotherapies. IgG4 does not fix complements, or internalize the target antigens, because IgG4 exists in a monovalent bispecific form in vivo. IgG4 autoantibodies can bock protein-protein interaction. Thus, the primary role of IgG4 anti-paranodal protein antibodies may be blockade of interactions between NF155 and CNTN1/CASPR1, leading to conduction failure, which is consistent with the sural nerve pathology presenting paranodal terminal loop detachment from axons with intact internodes in the absence of inflammation. However, it still remains to be elucidated how these autoantibodies belonging to the same IgG4 subclass can cause each IgG4 autoantibody-specific manifestation. Another important issue is to clarify the mechanism by which IgG4 antibodies to nodal/paranodal proteins emerge. IgG4 antibodies develop on chronic antigenic stimulation and can block antibodies that alleviate allergic inflammation by interfering with the binding of allergen-specific IgE to allergens. Thus, environmental antigens cross-reacting with nodal and paranodal proteins may warrant future study.

中文翻译：

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抗神经法素自身抗体和脱髓鞘作用。

涉及中枢和周围神经系统的脱髓鞘疾病在病因学上是异质的，细胞介导的和体液免疫均起着致病作用。最近，不仅在慢性脱髓鞘疾病的条件下，还发现了针对淋巴结和旁淋巴结蛋白的自身抗体，例如神经钙蛋白186（NF186），神经钙蛋白155（NF155），接触蛋白1（CNTN1），接触蛋白相关蛋白1（CASPR1）和神经胶质蛋白。作为多发性硬化症（MS）和慢性炎症性脱髓鞘性多发性神经根病，也可用于急性脱髓鞘性疾病，例如Guillain-Barré综合征。这些患者中只有一小部分具有抗结/旁结蛋白抗体。但是，这些自身抗体，尤其是针对偏执狂蛋白的IgG4亚类自身抗体，这些疾病具有独特的特征，这些疾病统称为结节病或偏执病。建立IgG4相关的结节病/偏瘫病的概念有助于诊断和治疗策略，因为IgG4自身抗体相关的神经系统疾病通常对常规免疫疗法无效。IgG4不能固定补体，也不能内化靶抗原，因为IgG4在体内以单价双特异性形式存在。IgG4自身抗体可以抑制蛋白质之间的相互作用。因此，IgG4抗寄生虫蛋白抗体的主要作用可能是阻断NF155和CNTN1 / CASPR1之间的相互作用，从而导致传导失败，这与腓肠神经病理学表现为淋巴结末端环脱离具有完整节间的轴突是一致的。炎症。然而，这些属于同一IgG4亚类的自身抗体如何引起每种IgG4自身抗体特异性表现仍然有待阐明。另一个重要问题是阐明针对淋巴结/旁淋巴结蛋白的IgG4抗体的出现机理。IgG4抗体是在慢性抗原刺激下产生的，可通过干扰变应原特异性IgE与变应原的结合来阻断减轻变应性炎症的抗体。因此，与淋巴结和旁淋巴结蛋白交叉反应的环境抗原可能值得进一步研究。IgG4抗体是在慢性抗原刺激下产生的，可通过干扰变应原特异性IgE与变应原的结合来阻断减轻变应性炎症的抗体。因此，与淋巴结和旁淋巴结蛋白交叉反应的环境抗原可能值得进一步研究。IgG4抗体是在慢性抗原刺激下产生的，可通过干扰变应原特异性IgE与变应原的结合来阻断减轻变应性炎症的抗体。因此，与淋巴结和旁淋巴结蛋白交叉反应的环境抗原可能值得进一步研究。