The Molecular Diagnosis of Streptococcal Infection is Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) and TS

Grant Type
Clinical
Grant Year
2002-2003
Institution Location
Foreign
Institution Organization Name
University College of London UK
Investigators Name
Giovannoni, Gavin, PhD

Sydenham’s chorea (SC), PANDAS and a small subset of patients with Tourette Syndrome (TS) have evidence of a recent or preceding streptococcal infection. Usually this infection is pharyngitis and/or tonsillitis. Commonly these patients have antibodies, that react with an area of the brain called the basal ganglia. These basal ganglia, at least in the case of SC, cross react with proteins on the surface of the streptococcal bacteria. This observation suggests they are induced by a process of molecular mimicry—that is when antibodies produced appropriately in response to streptococcal infection cross-react inappropriately with the basal ganglia. Because basal ganglia dysfunction is implicated in both the neurological and psychiatric manifestations of these disorders, it has been suggested that these antibodies may actually initiate or be responsible for causing these conditions. Unfortunately, the majority of patients come for treatment some time after their streptococcal infection. That is why it is difficult to culture streptococci from their routine throat swabs. Recent microbiology data have demonstrated that streptococci are difficult to eradicate, and probably remain latent within cells of the nasopharynx for prolonged periods of time. This may explain why so many people with TS have persistent serological evidence of streptococcal infection despite the lack of clinical evidence of recent infection. Therefore, we hypothesize that despite negative throat cultures, patients with these disorders may have persistent colonization of the nasopharynx with strains of streptococci that cause TS symptoms. Therefore, this persistent colonization is sufficient to maintain the inappropriate production of these cross-reactive antibodies, and hence the disorder—be it SC, PANDAS or TS—persists. We plan to use this award to develop molecular or DNA-based assays to diagnose streptococcal colonization in patients with these disorders and to establish a DNA database of the streptococcal organisms we find in these patients. This study will allow us to further explore the link between streptococcal infection and TS, and also develop methods to explore this link in a systematic way. This investigation will also help us to define the specific proteins in the basal ganglia that the streptococcal proteins mimic. Gavin Giovannoni, Ph.D., Institute of Neurology, University College London, Queens Square London, UK Award: $36,633 Tourette Association of America Inc. – Research Grant Award 2002-2003