Immunological Alterations in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Bessen, Debra, PhD

There is growing interest in the possible role of infectious agents and the accompanying immune response as triggers for a variety of neuropsychiatric disorders. Perhaps one of the most clear cut examples of a microbial-triggered, autoimmune-like disease involving the central nervous system is Sydenham’s chorea, a disorder of gross motor function that arises as a manifestation of rheumatic fever. Rheumatic fever can follow an inadequately treated group A streptococcal pharyngeal infection (i.e., “strep throat”) in a genetically predisposed host. It has been recently documented that at least some patients with Tourette Syndrome (TS) or obsessive-compulsive disorder (OCD) exhibit a group A streptococcal infection (or in some cases, a viral infection), concomitant with an acute exacerbation of neuropsychiatric symptoms. As with Sydenham’s chorea, TS and OCD involve basal ganglia dysfunction. Furthermore, there is a high prevalence of OCD symptoms in Sydenham’s chorea, and tics in OCD patients, suggesting that the three conditions might share a common etiology. Perhaps the most compelling evidence in support of the idea that TS and OCD can be triggered by group A streptococci comes from two independent reports demonstrating that the vast majority of patients with childhood-onset TS or OCD in those studies have elevated expression of a stable B-lymphocyte cell marker (D8/17) which also identifies close to 100% of rheumatic fever patients (with or without Sydenham’s chorea), but is present at low levels of expression only in healthy control populations and in patients with other autoimmune diseases. Two hypotheses have been put forth to explain the immunologic mechanism by which group A streptococci induce an autoimmune attack on healthy tissue: antigenic mimicry and superantigens. Elevated levels of antineuronal antibodies are observed in Sydenham’s chorea, TS and OCD, and anti-self antibodies that cross-react with group A streptococci antigens have also been described. Superantigens are produced by certain viruses and bacteria, including group A streptococci, and are potent stimulators of immune cells and inducers of inflammatory cytokine production, leading to an imbalance in T-lymphocyte cell networks that may contribute to autoimmune processes. The objective of this study is to establish whether or not immunological alterations in the peripheral blood accompany an increase in clinical severity in pediatric patients with TS. A longitudinal study of two cohorts—patients and controls—will assess, over time, fluctuations in gene expression in peripheral blood cells versus symptom severity. Blood will be collected from children with a history of TS at times reflecting asymptomatic, acute and convalescent stages of disease. Comparisons will be made between different stages of disease in individual patients and secondly, between patient and control groups. If immunological alterations associated with acute clinical onset are observed, then the exact nature of such alterations should provide insight as to the immunologic mechanisms involved and possibly, to the etiological bacterial factor(s) as well. Most importantly, this knowledge will provide a basis for a rational design of therapeutic and preventative interventions, such as antibiotic therapy or vaccines. Debra E. Bessen, Ph.D., James Leckman, M.D. and Malak Kotb (Co-Investigators) Yale University School of MedicineNew Haven, CT Award: $39,930 Tourette Association of America Inc. – Research Grant Award 1998