Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK.
Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK; Departments of Neurology and Neurosciences, Mayo Clinic, Jacksonville, FL, USA.
Rev Neurol (Paris). 2024 Nov;180(9):916-930. doi: 10.1016/j.neurol.2024.07.002. Epub 2024 Sep 16.
The past two decades have seen a considerable paradigm shift in the way autoimmune CNS disorders are considered, diagnosed, and treated; largely due to the discovery of novel autoantibodies directed at neuroglial surface or intracellular targets. This approach has enabled multiple bona fide CNS autoantibody-associated diseases to thoroughly infiltrate the sphere of clinical neurology, facilitating advances in patient outcomes. This review focusses on the fundamental immunological concepts behind CNS autoantibody-associated diseases. First, we briefly review the broad phenotypic profiles of these conditions. Next, we explore concepts around immune checkpoints and the related B cell lineage. Thirdly, the sources of autoantibody production are discussed alongside triggers of tolerance failure, including neoplasms, infections and iatrogenic therapies. Penultimately, the role of T cells and leucocyte trafficking into the CNS are reviewed. Finally, biological insights from responses to targeted immunotherapies in different CNS autoantibody-associated diseases are summarised. The continued and rapid expansion of the CNS autoantibody-associated field holds promise for further improved diagnostic and therapeutic paradigms, ultimately leading to further improvements in patient outcomes.
过去二十年中，人们对自身免疫性中枢神经系统疾病的认识、诊断和治疗方式发生了重大转变；这主要归因于对针对神经胶质表面或细胞内靶标的新型自身抗体的发现。这种方法使多种真正的中枢神经系统自身抗体相关疾病彻底渗透到临床神经学领域，促进了患者预后的改善。这篇综述聚焦于中枢神经系统自身抗体相关疾病背后的基本免疫学概念。首先，我们简要回顾了这些疾病的广泛表型特征。接下来，我们探讨了免疫检查点和相关 B 细胞谱系的概念。第三，讨论了自身抗体产生的来源以及包括肿瘤、感染和医源性治疗在内的耐受失败的触发因素。倒数第二，我们回顾了 T 细胞和白细胞向中枢神经系统的迁移作用。最后，总结了不同中枢神经系统自身抗体相关疾病中针对靶向免疫疗法的反应所带来的生物学见解。中枢神经系统自身抗体相关领域的持续快速扩展有望进一步改善诊断和治疗模式，最终改善患者的预后。
