Tourette综合征的免疫病理机制研究进展

doi:10.11852/zgetbjzz2020-2044

摘要/Abstract

摘要： 越来越多的研究关注Tourette 综合征(TS)免疫反应与其发病的关系,本文就TS的免疫病理机制进行综述。TS的疾病机制涉及神经与免疫系统功能失调的相互作用,免疫功能异常可能是TS异质性谱系障碍中某一特定亚群的特征。免疫细胞亚群、免疫细胞因子或基因的不同分布及表达会影响TS患者的免疫反应,多巴胺功能亢进、小胶质细胞活化增加、自身抗体参与TS发生的免疫病理机制。大样本的前瞻性研究将有助于进一步探讨TS的神经精神症状和免疫功能之间的关系。

关键词: Tourette综合征, 免疫, 调节性T细胞, 神经, 小胶质细胞

Abstract: Increasing studies focus on the association between immune reactions and the onset of Tourette syndrome (TS).This article reviews the immunological mechanism involved in the development of TS.Immune dysfunction plays an important role in the pathophysiology of TS and may be the characteristic of a specific subgroup in TS heterogeneity spectrum disorder.Different distribution and expression of immune cell subpopulations, immune cytokines or genes affect the immune response in patients with TS.Hyperdopamine function, increased microglia activation and autoantibodies are involved in the immunopathological mechanisms of TS development.Therefore, large-scale prospective studies are warranted to further explore the causal relationship between the neuropsychiatric symptoms and immune dysfunction of TS.

Key words: Tourette syndrome, immunity, regulatory T cells, nerve, microglia

中图分类号:

R749.94

张小玲, 刘秀梅. Tourette综合征的免疫病理机制研究进展[J]. 中国儿童保健杂志, 2022, 30(4): 409-412.

ZHANG Xiao-ling, LIU Xiu-mei. Research advances in immunopathological mechanism of Tourette syndrome[J]. Chinese Journal of Child Health Care, 2022, 30(4): 409-412.

参考文献

[1] Scharf JM, Miller LL, Gauvin CA, et al.Population prevalence of Tourette syndrome:A systematic review and meta-analysis[J] .2015, 30(2): 221-228.
[2] Tsetsos F, Yu D, Sul JH, et al.Synaptic processes and immune-related pathways implicated in Tourette syndrome [J].Transl Psychiatry, 2021, 11(1):56.
[3] Kawikova I, Leckman JF, Kronig H, et al.Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome:A preliminary study [J].Biol Psychiatry, 2007, 61(3): 273-278.
[4] Yildirim Z, Karabekiroglu K, Yildiran A, et al.An examination of the relationship between regulatory T cells and symptom flare-ups in children and adolescents diagnosed with chronic tic disorder and Tourette syndrome[J] .Nord J Psychiatry, 2021,75(1):18-24.
[5] Wing JB,Tay C, Sakaguchi S, et al.Control of Regulatory T Cells by Co-signal Molecules[J].Adv Exp Med Biol, 2019, 1189:179-210.
[6] Leckman JF, Katsovich L, Kawikova I, et al.Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome[J].Biol Psychiatry, 2005, 57(6): 667-673.
[7] Parker-Athill EC, Ehrhart J, Tan J,et al.Cytokine correlations in youth with tic disorders[J] .J Child Adolesc Psychopharmacol, 2015, 25(1): 86-92.
[8] Yeon SM, Lee JH, Kang D, et al.A cytokine study of pediatric Tourette's disorder without obsessive compulsive disorder[J].Psychiatry Res, 2017, 247: 90-96.
[9] Frick LR,Rapanelli M, Jindachomthong K, et al.Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum[J].Brain Behav Immun, 2018, 69: 304-311.
[10] Baumgaertel C, Skripuletz T, Kronenberg J, et al.Immunity in Gilles de la Tourette-Syndrome:Results from a cerebrospinal fluid study[J].Front Neurol, 2019, 10: 732.
[11] Dalsgaard S, Waltoft BL, Leckman JF, et al.Maternal history of autoimmune disease and later development of tourette syndrome in offspring[J].J Am Acad Child Adolesc Psychiatry, 2015, 54(6):495-501.
[12] Giannoccaro MP, Wright SK, Vincent A.In vivo mechanisms of antibody-mediated neurological disorders:Animal models and potential implications[J].Front Neurol, 2020, 10: 1394.
[13] Tay TL, Savage JC, Hui CW, et al.Microglia across the lifespan: from origin to function in brain development, plasticity and cognition [J].J Physiol (Lond), 2017, 595(6): 1929-1945.
[14] Nagarajan N,Jones BW,West PJ, et al.Corticostriatal circuit defects in Hoxb8 mutant mice[J].Mol Psychiatry, 2018, 23(9), 1868-1877.
[15] Frick L,Rapanelli M, Abbasi E, et al.Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation[J].Brain Behav Immun, 2016, 57: 326-337.
[16] Lennington JB, Coppola G, Kataoka-Sasaki Y, et al.Transcriptome analysis of the human striatum in Tourette syndrome[J].Biol Psychiatry, 2016, 79(5), 372-382.
[17] Kumar A, Williams MT.Chugani HT.Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and Tourette syndrome:A positron emission tomographic (PET) study using 11C-[R]-PK11195[J].J Child Neurol, 2015, 30(6): 749-756.
[18] Thomas Broome S, Louangaphay K, Keay KA, et al.Dopamine:An immune transmitter[J].Neural Regen Res, 2020, 15(12): 2173-2185.
[19] Elgueta D, Contreras F, Prado C, et al.Dopamine receptor D3 expression is altered in CD4+ T-cells from parkinson's disease patients and its pharmacologic inhibition attenuates the motor impairment in a mouse model[J] .Front Immunol, 2019, 10: 981.
[20] Levite M, Marino F,Cosentino M. Dopamine, T cells and multiple sclerosis (MS) [J].J Neural Transm (Vienna), 2017, 124(5): 525-542.
[21] Addabbo F, Baglioni V, Schrag A, et al.Anti-dopamine D2 receptor antibodies in chronic tic disorders:Potential link to fluctuations of tic severity[J].Dev Med Child Neurol, 2020, 62: 1205-1212.
[22] Levite M.Dopamine and T cells: dopamine receptors andpotent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases[J].Acta Physiol(Oxf), 2016, 216(1): 42-89.
[23] Wu C, Qin X, Du H, et al.The immunological function of GABAergic system[J].Front Biosci (Landmark Ed), 2017, 22: 1162-1172.
[24] Pogorelov V, Xu M, Smith HR, et al.Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition[J].Exp Neurol, 2015, 265: 122-128.
[25] Perlmutter SJ, Leitman SF, Garvey MA, et al.Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood[J] .Lancet, 1999, 354(9185): 1153-1158.
[26] Williams KA,Swedo SE, Farmer CA, et al.Randomized, controlled trial of intravenous immunoglobulin for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections[J].J Am Acad Child Adolesc Psychiatry, 2016, 55(10): 860-867.
[27] Zykov VP, Shcherbina AY, Novikova EB, et al.Neuroimmune aspects of the pathogenesis of Tourette's syndrome and experience in the use of immunoglobulins in children [J].Neurosci Behav Physiol, 2009, 39(7): 635-638.
[28] Hoekstra PJ,Minderaa RB, Kallenberg CG.Lack of effect of intravenous immunoglobulins on tics:A double-blind placebo-controlled study[J].J Clin Psychiatry, 2004, 65(4): 537-542.