Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, UK.
Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, UK.
Neuropharmacology. 2018 Apr;132:71-82. doi: 10.1016/j.neuropharm.2017.04.046. Epub 2017 May 3.
The field of neuronal autoantibody associated diseases of the central nervous system has expanded dramatically in the last few years. The range of identified neuronal and glial antibody targets has led to the accurate classification of a number of syndromes which each associate with characteristic clinical features. These diseases are especially important due to their frequent response to immunotherapies. Antibodies against the N-methyl, d-aspartate receptor (NMDAR) and leucine-rich glioma inactivated 1 (LGI1) are the commonest autoantibodies known in patients with autoimmune forms of encephalitis. Patients with NMDAR-antibodies often present with psychiatric symptoms and a movement disorder, whereas patients with LGI1-antibodies have frequent seizures and prominent amnesia. In contrast, aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies are found in patients with inflammation of the spine and optic nerves. The antigenic-specificities appear to determine the associated clinical syndromes, hence the detection of these antibodies informs clinical practice and the biology of these diseases. Indeed, the mechanisms of antibody action are being intensively studied in vitro and in vivo. Overall, these studies confirm the pathogenic potential of the antibodies, and suggest antigen internalisation and complement fixation are the two dominant mechanisms of pathogenicity, and that their relative contributions vary between conditions. In addition to discussing the antigenic targets, the associated clinical features and mechanisms of antibodies, we review the current and future immunotherapy strategies which aim to optimise patient outcomes. This article is part of the Special Issue entitled 'Channelopathies.'
中枢神经系统神经元自身抗体相关疾病领域在过去几年中迅速发展。已鉴定的神经元和神经胶质抗体靶标范围导致了许多综合征的准确分类，这些综合征每个都与特征性的临床特征相关联。这些疾病非常重要，因为它们经常对免疫疗法有反应。针对 N-甲基-D-天冬氨酸受体 (NMDAR) 和富含亮氨酸胶质瘤失活 1 型 (LGI1) 的抗体是自身免疫性脑炎患者中最常见的自身抗体。NMDAR 抗体患者常出现精神症状和运动障碍，而 LGI1 抗体患者常出现癫痫发作和明显的健忘症。相比之下，水通道蛋白 4 和髓鞘少突胶质细胞糖蛋白抗体存在于脊柱和视神经炎症的患者中。抗原特异性似乎决定了相关的临床综合征，因此这些抗体的检测为临床实践和这些疾病的生物学提供了信息。事实上，抗体的作用机制正在体外和体内进行深入研究。总的来说，这些研究证实了抗体的致病性潜力，并表明抗体内化和补体固定是两种主要的致病性机制，它们在不同的条件下的相对贡献有所不同。除了讨论抗原靶标、相关的临床特征和抗体机制外，我们还回顾了当前和未来的免疫治疗策略，旨在优化患者的治疗效果。本文是题为“通道病”的特刊的一部分。
