Autoantibodies and Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Johns Hopkins University
Investigators Name
Singer, Harvey, MD

There is accumulating evidence suggesting that environmental (non-genetic factors) may have either an etiologic role or one that mediates the form and/or severity of tics. For example, tics have appeared in association with a variety of acute and chronic neurologic disorders, such as herpes encephalitis, head injury, stroke, and the use of drugs. Additionally, if solely caused by genetic factors, twins with the same genes (monozygotic, MZ) would be expected to have similar clinical symptomatology. In two separate studies of MZ twin pairs, however, the concordance rate for TS and/or tic disorder was less than 100%. Furthermore, these twin pairs, despite inheritance of similar genetic material, showed marked variability in the severity of their tics. A variety of evidence suggests that there may be an association among streptococcal infections, the production of antibodies against brain cells (anti-neuronal antibodies), and the induction or exacerbation of tic disorders. Supporting data include the following: a well established relationship between streptococcal infections, autoantibodies, and a movement disorder known as Sydenham’s chorea; observations by several investigators showing a temporal relationship between streptococcal illness and the abrupt onset of tics; studies by Dr. Kiessling and co-workers indicating that serum antibodies against brain cells were present more frequently in children with movement disorders and in those with attention deficit hyperactivity disorder (ADHD) plus obsessive compulsive behaviors (OCB), and lastly, others have suggested a possible association between TS and the presence of antiphospholipid antibodies — antibodies directed against negatively charged phospholipids found in brain cells. In our research project, 40 children with TS between the ages of 7 to 16 years and 40 control children will undergo careful characterization of existing symptoms (tics, ADHD, OCB, behavior problems) and prior infections. Those fulfilling eligibility criteria will have blood drawn for laboratory studies. All samples will be coded and investigators performing laboratory assays will not be aware of subject diagnosis. Studies on blood will include assays for anti-neuronal antibodies (ELISA and Western blot analyses), evidence for streptococcal infection (ASO titers and antiDNAase B), and the presence of other antibodies (antinuclear and antiphospholipid). We hypothesize that antineuronal antibodies will be found more frequently in patients with TS than in an age-matched control population, thereby supporting a non-genetic role. We further predict that those subjects with antineuronal antibodies will have significant differences in the type and frequency of their tics. We further expect to find that antiphospholipid antibodies will not be significantly associated with TS. Lastly, this study will provide further information on whether the antineuronal antibodies detected in patients with movement disorders are associated with streptococcal infections. Harvey S. Singer, M.D., The Johns Hopkins University, Baltimore, MD Louise Kiessling, M.D., Brown University Pawtucket, RI Award $25,000 Tourette Association of America Inc. – Research Grant Award 1995