治疗神经自身免疫性疾病:生物标志物、免疫机制和治疗靶点。

IF 14.7 1区 医学 Q1 NEUROSCIENCES Neuron Pub Date : 2025-02-05 Epub Date: 2025-01-13 DOI:10.1016/j.neuron.2024.12.006
Yahel Segal, John Soltys, Benjamin D S Clarkson, Charles L Howe, Sarosh R Irani, Sean J Pittock
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引用次数: 0

摘要

自身免疫神经学是一个迅速发展的领域,由神经胶质自身抗体的发现驱动,包括影响神经系统各个层面的无数条件。传统上,靶向细胞内抗原的自身抗体被认为是T细胞介导的细胞毒性的标志物,而靶向细胞外抗原的自身抗体被认为是疾病的致病驱动因素。然而,最近的进展强调了这些免疫机制之间复杂的相互作用,表明免疫发病机制是连续的。免疫耐受的破坏是这些疾病的核心,受到遗传易感性、感染和恶性肿瘤等可改变和不可改变的风险因素的影响。虽然重大的治疗进展已经彻底改变了某些疾病的治疗,如视神经脊髓炎,但我们对许多其他疾病的理解,特别是T细胞介导的疾病,仍然有限,可用的治疗方案较少。未来的研究应侧重于改善效应函数建模和加深我们对免疫耐受影响因素的理解,以提供新的治疗方案和改善患者护理。
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Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.

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.

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来源期刊
Neuron
Neuron 医学-神经科学
CiteScore
24.50
自引率
3.10%
发文量
382
审稿时长
1 months
期刊介绍: Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.
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