Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals Foundation Trust, Oxford, United Kingdom.
Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals Foundation Trust, Oxford, United Kingdom.
Handb Clin Neurol. 2024;203:235-269. doi: 10.1016/B978-0-323-90820-7.00005-7.
The autoimmune channelopathies represent a rapidly evolving scientific and clinical domain. The description of channels, expressed on neurons and glia, as targets of autoantibodies in neuromyelitis optica, autoimmune encephalitis, and related syndromes have revolutionized many areas of neurologic practice. To date, tens of surface antibody specificities have been described, a number that is likely to continue to increase. A central paradigm for all these disorders is that of pathogenic autoantibodies which target extracellular epitopes accessible for binding in vivo. Hence, in these disorders, the autoantibodies are causative diagnostic tools, and provide valuable reagents to model the diseases. Their production by B-lineage cells provides opportunities to study and modulate their production. Across these syndromes, early recognition and treatment are critical since most respond to immunotherapies. Yet, several unmet medical needs persist within treated patient populations, and widespread clinical under-recognition remains a challenge. In this review, we summarize the neuroscience and immunologic basis of autoantibody-mediated central nervous system channelopathies, the molecular effects of the autoantibodies, clinical phenotypes, and treatment approaches. We describe progress since the inauguration of the field through to open questions and potential future directions.
自身免疫性通道病是一个快速发展的科学和临床领域。在视神经脊髓炎、自身免疫性脑炎和相关综合征中，描述神经元和神经胶质上表达的通道作为自身抗体的靶标，这一发现彻底改变了许多神经科的临床实践。迄今为止，已经描述了数十种表面抗体特异性，而且这个数字可能还会继续增加。所有这些疾病的一个核心范式是致病性自身抗体靶向体内可结合的细胞外表位。因此，在这些疾病中，自身抗体是致病的诊断工具，并为疾病模型提供了有价值的试剂。它们由 B 细胞谱系产生，为研究和调节其产生提供了机会。在这些综合征中，早期识别和治疗至关重要，因为大多数对免疫疗法有反应。然而，在接受治疗的患者群体中仍存在一些未满足的医疗需求，广泛的临床认识不足仍然是一个挑战。在这篇综述中，我们总结了自身抗体介导的中枢神经系统通道病的神经科学和免疫学基础、自身抗体的分子作用、临床表型和治疗方法。我们描述了该领域自成立以来的进展，以及尚未解决的问题和潜在的未来方向。
