Martino Davide, Dale Russell C, Gilbert Donald L, Giovannoni Gavin, Leckman James F
Department of Neurological and Psychiatric Sciences, University of Bari, Italy.
Mov Disord. 2009 Jul 15;24(9):1267-79. doi: 10.1002/mds.22504.
Tourette syndrome (TS) has a multifactorial etiology, in which genetic, environmental, immunological and hormonal factors interact to establish vulnerability. This review: (i) summarizes research exploring the exposure of TS patients to immune-activating environmental factors, and (ii) focuses on recent findings supporting a role of the innate and adaptive immune systems in the pathogenesis of TS and related disorders. A higher exposure prior to disease onset to group A beta-haemolytic streptococcal (GABHS) infections in children with tics and obsessive-compulsive (OC) symptoms has been documented, although their influence upon the course of disease remains uncertain. Increased activation of immune responses in TS is suggested by changes in gene expression profiles of peripheral immune cells, relative frequency of lymphocyte subpopulations, and synthesis of immune effector molecules. Increased activity of cell-mediated mechanisms is suggested by the increased expression of genes controlling natural killer and cytotoxic T cells, increased plasma levels of some pro-inflammatory cytokines which correlate with disease severity, and increased synthesis of antineuronal antibodies. Important methodological differences might account for some inconsistency among results of studies addressing autoantibodies in TS. Finally, a general predisposition to autoimmune responses in TS patients is indicated by the reduced frequency of regulatory T cells, which induce tolerance towards self-antigens. Although the pathogenic role of immune activation in TS has not been definitively proven, a pathophysiological model is proposed to explain the possible effect of immunity upon dopamine transmission regulation and the generation of tics.
抽动秽语综合征（TS）病因多因素，其中遗传、环境、免疫和激素因素相互作用导致易感性。本综述：（i）总结了探索TS患者暴露于免疫激活环境因素的研究，（ii）重点关注支持先天和适应性免疫系统在TS及相关疾病发病机制中作用的最新发现。已有文献记载，患有抽动和强迫症状（OC）的儿童在疾病发作前更高频率地暴露于A组β溶血性链球菌（GABHS）感染，尽管其对疾病进程的影响仍不确定。外周免疫细胞基因表达谱的变化、淋巴细胞亚群的相对频率以及免疫效应分子的合成表明TS中免疫反应的激活增加。控制自然杀伤细胞和细胞毒性T细胞的基因表达增加、一些与疾病严重程度相关的促炎细胞因子血浆水平升高以及抗神经元抗体合成增加，提示细胞介导机制的活性增加。重要的方法学差异可能解释了TS中自身抗体研究结果之间的一些不一致。最后，调节性T细胞频率降低表明TS患者普遍存在自身免疫反应易感性，调节性T细胞可诱导对自身抗原的耐受性。尽管免疫激活在TS中的致病作用尚未得到明确证实，但提出了一个病理生理模型来解释免疫对多巴胺传递调节和抽动产生的可能影响。
