Department of Neurology - Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Münster, Germany.
Curr Opin Neurol. 2012 Jun;25(3):341-8. doi: 10.1097/WCO.0b013e3283531efb.
The human central nervous system (CNS) can mistakenly be the target of adaptive cellular and humoral immune responses causing both functional and structural impairment. We here provide an overview of neuron-directed autoimmunity as a novel class of inflammatory CNS disorders, their differential diagnoses, clinical hallmarks, imaging features, characteristic laboratory, electrophysiological, cerebrospinal fluid and neuropathological findings, cellular and molecular disease mechanisms, as well as therapeutic options.
A growing number of immune-mediated CNS disorders of both autoimmune and paraneoplastic origin have emerged, in which neurons seem to be the target of the immune response. Antibodies binding to a variety of synaptic and extrasynaptic antigens located on the neuronal surface membrane can define distinct entities. Clinically, these disorders are characterized by subacute CNS-related [and sometimes peripheral nervous system (PNS)-related] symptoms involving a variety of cortical and subcortical gray matter areas, which often reflect the expression pattern and function of the respective target antigen. Antibodies seem to be pathogenic and cause (reversible) disturbance of synaptic transmission and neuronal excitability by selective functional inhibition or crosslinking and internalization of their antigen in the absence of overt cytotoxicity, at least at early disease stages. Whether at later disease stages antibody-mediated cytotoxicity, cytotoxic CD8+ T cells, or other detrimental immune mechanisms contribute to neuronal impairment is unclear at present.
Adaptive humoral autoimmunity directed to neuronal cell-surface antigens offers first and unique insights and provokes further investigation into the systemic, cellular, and molecular consequences of immune-mediated disruption of distinct neuronal signaling pathways within the living human CNS.
人体中枢神经系统（CNS）可能会错误地成为适应性细胞和体液免疫反应的靶标，导致功能和结构损伤。本文概述了神经元定向自身免疫作为一类新型炎症性 CNS 疾病，其鉴别诊断、临床特征、影像学特征、特征性实验室、电生理学、脑脊液和神经病理学发现、细胞和分子疾病机制以及治疗选择。
越来越多的自身免疫和副肿瘤来源的免疫介导的 CNS 疾病已经出现，其中神经元似乎是免疫反应的靶标。结合位于神经元表面膜上的各种突触和 extrasynaptic 抗原的抗体可以定义不同的实体。临床上，这些疾病的特征是亚急性 CNS 相关（有时是周围神经系统（PNS）相关）症状，涉及多种皮质和皮质下灰质区域，这些症状通常反映了各自靶抗原的表达模式和功能。抗体似乎具有致病性，并通过选择性的功能抑制或抗原的交联和内化导致（可逆的）突触传递和神经元兴奋性紊乱，而没有明显的细胞毒性，至少在疾病早期阶段是如此。在疾病的后期阶段，抗体介导的细胞毒性、细胞毒性 CD8+T 细胞或其他有害免疫机制是否有助于神经元损伤目前尚不清楚。
总之，针对神经元细胞表面抗原的适应性体液自身免疫提供了第一个独特的见解，并促使进一步研究免疫介导的对活体内人类 CNS 中不同神经元信号通路的系统性、细胞性和分子性破坏的后果。
