Martino Davide, Zis Panagiotis, Buttiglione Maura
Neurology Department, King's College Hospital, London, UK; Queen Elizabeth Hospital, Woolwich, London, UK; Centre for Neuroscience and Trauma, Queen Mary University of London, London, UK.
Neurology Department, King's College Hospital, London, UK.
Brain Res. 2015 Aug 18;1617:126-43. doi: 10.1016/j.brainres.2014.04.027. Epub 2014 May 15.
Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.
抽动秽语综合征（TS）是一种起病于儿童期的抽动障碍，与参与感觉和运动处理的脑网络异常发育有关。有人提出免疫机制参与了其病理生理过程。基于用细菌或病毒模拟物进行主动免疫、直接注射细胞因子或患者血清抗神经元抗体建立的动物模型，以及转基因方法，重现了人类TS中观察到的刻板行为。动物模型提出了小胶质细胞在TS及相关疾病的神经免疫相互作用中的关键作用，并得到了最近尸检研究的证实。与自闭症类似，遗传和早期生活环境因素可能促使免疫机制参与TS中假定的异常发育轨迹，并导致这种情况下的全身免疫失调。临床研究表明TS与对A组链球菌（GAS）等病原体的免疫反应之间存在关联，尽管它们作为风险调节因子的作用仍不明确。探索细胞因子和免疫球蛋白水平、免疫细胞亚群以及外周淋巴细胞基因表达谱的临床研究表明，全身水平的免疫反应过度活跃。另一方面，自身抗体的参与仍不确定，需要使用基于活细胞的方法进行更多研究。总体而言，大量证据支持这样一种假说，即TS的疾病机制与其他神经发育疾病（如自闭症）一样，可能涉及功能失调的神经免疫相互作用，最终导致控制不同行为领域的脑通路成熟改变，并可能导致免疫和应激反应组织方式的差异。本文是名为“健康与疾病中的神经免疫学”特刊的一部分。
