The role of immune mechanisms in Tourette syndrome

Brain Res. 2015 Aug 18:1617:126-43. doi: 10.1016/j.brainres.2014.04.027. Epub 2014 May 15.

Abstract

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.

Keywords: Autoantibody; Cytokine; Immunization; Immunoglobulin; Lymphocyte; Microglia; Tourette syndrome; Transcriptomic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / complications
  • Brain / immunology
  • Brain / metabolism
  • Disease Models, Animal
  • Encephalitis / complications
  • Encephalitis / genetics
  • Environment
  • Humans
  • Inflammation / complications
  • Inflammation / genetics
  • Tourette Syndrome / etiology*
  • Tourette Syndrome / genetics
  • Tourette Syndrome / immunology*
  • Tourette Syndrome / metabolism