Immunopathogenic mechanisms in tourette syndrome: A critical review.
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.
Department of Neurological and Psychiatric Sciences, University of Bari, Italy. davidemartino@virgilio.it
Davide
D
Martino
Russell C
RC
Dale
Donald L
DL
Gilbert
Gavin
G
Giovannoni
James F
JF
Leckman
D001323:Autoantibodies / Q000378:metabolism; D004777:Environment; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology*; D018448:Models, Immunological; D013315:Stress, Psychological / Q000276:immunology; D005879:Tourette Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D001323:Autoantibodies