Segal Yahel, Soltys John, Clarkson Benjamin D S, Howe Charles L, Irani Sarosh R, Pittock Sean J
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Neurosciences, Mayo Clinic, Jacksonville, FL, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
Neuron. 2025 Feb 5;113(3):345-379. doi: 10.1016/j.neuron.2024.12.006. Epub 2025 Jan 13.
Autoimmune neurology is a rapidly expanding field driven by the discovery of neuroglial autoantibodies and encompassing a myriad of conditions affecting every level of the nervous system. Traditionally, autoantibodies targeting intracellular antigens are considered markers of T cell-mediated cytotoxicity, while those targeting extracellular antigens are viewed as pathogenic drivers of disease. However, recent advances highlight complex interactions between these immune mechanisms, suggesting a continuum of immunopathogenesis. The breakdown of immune tolerance, central to these conditions, is affected by modifiable and non-modifiable risk factors such as genetic predisposition, infections, and malignancy. While significant therapeutic advancements have revolutionized treatment of certain diseases, such as neuromyelitis optica, our understanding of many others, particularly T cell-mediated conditions, remains limited, with fewer treatment options available. Future research should focus on improving effector function modeling and deepening our understanding of the factors influencing immune tolerance, with the goal of providing novel treatment options and improving patient care.
自身免疫性神经病学是一个迅速发展的领域，由神经胶质自身抗体的发现所推动，涵盖了影响神经系统各个层面的众多病症。传统上，靶向细胞内抗原的自身抗体被视为T细胞介导的细胞毒性标志物，而靶向细胞外抗原的自身抗体则被视为疾病的致病驱动因素。然而，最近的进展凸显了这些免疫机制之间的复杂相互作用，提示了免疫发病机制的连续性。免疫耐受的破坏是这些病症的核心，受到可改变和不可改变的风险因素的影响，如遗传易感性、感染和恶性肿瘤。虽然重大的治疗进展已经彻底改变了某些疾病的治疗方式，如视神经脊髓炎，但我们对许多其他疾病，特别是T细胞介导的病症的理解仍然有限，可用的治疗选择较少。未来的研究应专注于改进效应器功能建模，并加深我们对影响免疫耐受的因素的理解，目标是提供新的治疗选择并改善患者护理。
