Investigations in the last 10 years have revealed a new category of neurological diseases mediated by antibodies against cell surface and synaptic proteins. There are currently 16 such diseases all characterized by autoantibodies against neuronal proteins involved in synaptic signaling and plasticity. In clinical practice these findings have changed the diagnostic and treatment approach to potentially lethal, but now treatable, neurological and psychiatric syndromes previously considered idiopathic or not even suspected to be immune-mediated. Studies show that patients' antibodies can impair the surface dynamics of the target receptors eliminating them from synapses (e.g., NMDA receptor), block the function of the antigens without changing their synaptic density (e.g., GABAb receptor), interfere with synaptic protein-protein interactions (LGI1, Caspr2), alter synapse formation (e.g., neurexin-3α), or by unclear mechanisms associate to a new form of tauopathy (IgLON5). Here we first trace the process of discovery of these diseases, describing the triggers and symptoms related to each autoantigen, and then review in detail the structural and functional alterations caused by the autoantibodies with special emphasis in those (NMDA receptor, amphiphysin) that have been modeled in animals.

中文翻译：

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中枢神经系统自身免疫性疾病中突触受体和神经细胞表面蛋白的自身抗体。


过去十年的研究揭示了一种新的神经系统疾病类别，由针对细胞表面和突触蛋白的抗体介导。目前有 16 种此类疾病，其特征都是针对参与突触信号传导和可塑性的神经元蛋白的自身抗体。在临床实践中，这些发现改变了诊断和治疗方法，使以前被认为是特发性或什至不怀疑是免疫介导的神经和精神综合征可能致命，但现在可以治疗。研究表明，患者的抗体可以损害目标受体的表面动力学，将其从突触中消除（例如，NMDA 受体），阻断抗原的功能而不改变其突触密度（例如，GABAb 受体），干扰突触蛋白-蛋白相互作用（LGI1、Caspr2）、改变突触形成（例如 neurexin-3α）或通过与新形式的 tau 蛋白病（IgLON5）相关的不清楚机制。在这里，我们首先追溯这些疾病的发现过程，描述与每种自身抗原相关的触发因素和症状，然后详细回顾由自身抗体引起的结构和功能改变，特别强调那些已被研究的自身抗体（NMDA 受体、两性蛋白）。以动物为模型。