Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy.
Mov Disord. 2018 Sep;33(9):1376-1389. doi: 10.1002/mds.27446. Epub 2018 Sep 14.
An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody-mediated movement disorders, and outline increasingly well-established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally-driven immune responses may reach the central nervous system. We integrate this with the immunologically-relevant clinical observations of preceding infections, tumours and human leucocyte antigen-associations to provide an overview of the therapeutically-relevant underlying adaptive immunology in the autoantibody-mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
越来越多的运动障碍与自身抗体有关。这些自身抗体中的许多靶向神经元表面蛋白的细胞外结构域，并与高度特异性表型相关，这表明它们具有潜在的致病性。下面，我们描述了一些更常见的自身抗体介导的运动障碍相关的表型，并概述了越来越明确的自身抗体致病性机制，包括抗原下调和补体固定。尽管取得了这些进展，以及随着免疫疗法的早期升级，临床结果明显改善的证据越来越多，但这些疾病的细胞免疫基础仍未得到充分关注。因此，在这里，我们概述了 T 细胞和 B 细胞在自身抗体产生中的可能作用，并思考了这些作用如何指导当前的免疫治疗方案以及我们未来对该领域精准医学的理解。此外，我们总结了这些外周驱动的免疫反应可能到达中枢神经系统的潜在机制。我们将其与先前感染、肿瘤和人类白细胞抗原相关性的免疫相关临床观察结果相结合，提供了自身抗体介导的运动障碍中治疗相关适应性免疫的概述。© 2018 作者。运动障碍由 Wiley Periodicals, Inc. 代表国际帕金森病和运动障碍协会出版。
