Role of Bacterial Superantigens in Tourette syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Tennessee
Investigators Name
Kotb, Malak, PhD

There is an increasing recognition of a role for both viral and bacterial pathogens in triggering autoimmune attacks. Theoretically, infectious agents can participate in any of the three stages of autoimmune diseases: initiation, propagation and tissue destruction. Several hypotheses have been proposed to explain the mechanism linking infection with certain pathogens to specific autoimmune diseases. One of the hypotheses suggests that infectious agents produce substances that activate the immune system in a way that leads to aberrant stimulation of the immune system, and the generation of pathological autoreactive immune cells that can attack tissues and damage organs. Recently, it has been proposed that at least some people with Tourette Syndrome (TS) exhibit a group A?-hemolytic streptococcal (GA?HS) infection concomitant with an acute exacerbation of tic symptoms. It is well-established that primary infection with GA?HS can lead to a number of autoimmune sequelae, including rheumatic fever and Sydenham’s chorea which, like TS, involve the basal ganglia. In addition, a ? cell marker associated with rheumatic fever patients was also detected on ? cells from a significant number of TS patients. These data suggest that streptococcal infection may have a role in inducing or exacerbating TS in some individuals. A group of immunologists, microbiologists and psychiatrists at the University of Tennessee and Yale University have teamed up to investigate the possible role of bacterial infection in the pathogenesis of TS. The study focuses on the possible role of bacterial superantigens in triggering or exacerbating TS. Superantigens have been implicated in the pathogenesis of a number of autoimmune diseases. Exposure to superantigens can lead to specific patterns of skewing in the peripheral blood T cell repertoire, thereby allowing the detection and identification of specific superantigens. Our studies should determine if superantigens are involved in episodes of acute exacerbation of TS and may lead to a better understanding of disease pathogenesis and the development of directed therapeutic strategies. The aims of the proposed study are: 1) to determine whether changes in the T cell repertoire of individual patients are associated with clinical manifestations of TS; 2) to determine whether all (or most) TS patients have in common a particular pattern of specific repertoire skewing; and 3) to identify bacterial strains that are possible triggers for acute exacerbations of TS. We anticipate that the findings of this study will provide guidance in the design of further studies on TS, lead to a better understanding of the disease process, and allow for the design of effective therapeutic and preventive strategies. Malak Kotb, Ph.D. Debra E. Bessen, Ph.D. University of Tennessee/ Virginia Medical Center Memphis, TN James F. Leckman, M.D. (Collaborator), Yale University, New Haven, CT Award: $39,930 Tourette Association of America Inc. – Research Grant Award 1997