Characterization of Lymphocytic Diversity in Children with Tic Exacerbations

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Florida
Investigators Name
Murphy, Tanya, MD

Identification of patients who are at risk for immune mediated neuropsychiatric disorders will improve the likelihood of appropriate preventive therapies. Reports are mounting to support a role of Group A streptococcus (GAS) in children with tic disorders. Symptoms seen in Sydenham’s chorea (SC), the neurological consequence of some GAS infections, are on the continuum of those seen in children with tic disorders. One of the major differences in these two illnesses is the character of the course of illness. SC is usually self limited, but Tourette Syndrome has a more chronic and changing course. The mechanism that causes tic exacerbations is unknown. Stress and illness are two easily recognized triggers. Our hypothesis is that a marked increase in symptoms is due to immune activation that could be caused by illness or stress. Although prevailing theories suggest that SC and immune triggered tic symptoms are primarily antibody mediated, recent neuroimmunological research suggests that lymphocytes traffic across the blood brain barrier. T cell mediated immune activation and cellular death could lead to loss of B cell tolerance and thus to a secondary autoimmune response. Infections that produce molecular mimicry at an early stage may alter the development of a normal T cell repertoire and lead to cellular activation with poor modulation of the cytokine response. Symptom exacerbations, triggered either by strep or by other infections, may be mediated by mechanisms that involve T cell activation and cytokine release. One way of assessing vulnerability to cell-mediated CNS autoimmunity is by examining peripheral lymphocyte subsets/ activation markers and by assessing the level of T cell differentiation. We believe that a more specific method of examining effects of environmental and innate alterations of lymphocyte populations is by measuring clonality of the variable region of the beta chain (Vß) of the T cell receptor. This region is one of the key antigen-binding sites active during a typical immune response. The genetic composition of this region is modified during the interaction with an antigen and can lead to an oligoclonal, monoclonal, or polyclonal expansion of one or more Vß components. The genetic variability of this region of the T cell receptor can be measured in patients and compared with a control group. Lymphocytic characterizations have not been determined in children with tics nor have they previously been correlated to strep mediated neuropsychiatric symptoms. Our goal is to determine whether immune activation exists during exacerbations and, if so, characterize the lymphocytic phenotype. Tanya K. Murphy, M.D., McKnight Brain Institute University of Florida, Child Tic & Anxiety Disorder Clinic, Gainesville, FL Award: $71,254 Tourette Association of America Inc. – Research Grant Award 2002-2003