Case-control, exploratory study of cerebrospinal fluid chemokines/cytokines and lymphocyte subsets in childhood Tourette syndrome with positive streptococcal markers

Abstract

A longstanding question is whether neuroinflammation is present in children symptomatic for Tourette syndrome (TS) with positive streptococcal serology and throat cultures. The objective was to directly test for it using modern hypothesis-driven approaches. Profiling studies for 14 immune cell types (flow cytometry), 7 chemokines/cytokines (ELISA), oligoclonal bands, and other immunoglobulins were performed in this IRB-approved study of 5 children with TS and streptococcal markers compared to data from 26 non-inflammatory pediatric neurological controls. Subjects were well-characterized clinically and with standardized scales for tics and obsessions/compulsions. Three subjects with TS (60%) had positive throat cultures for Group A beta-hemolytic strep, five had elevated anti-deoxyribonuclease-B titers (mean=444), and 4 (80%) had elevated anti-streptolysin O titers (981). There were no significant differences between groups in the frequency of CSF B and T cell subsets or NK cells; the proportion of intracellularly-stained T helper type 1 (IFN-γ) or type 2 (IL-4) cells; the concentrations of B cell chemoattractants CXCL13, CXCL10; the B cell proliferation/survival cytokines BAFF and APRIL, or other chemokines (CCL19, CCL21, CCL22). None of the patients had positive CSF oligoclonal bands or an abnormal IgG index/synthesis rate. Parallel blood studies were negative. This novel study found no group CSF lymphocyte phenotypic abnormalities or elevated inflammatory mediators in childhood TS despite positive serology and throat cultures for Group A beta-hemolytic streptococci. It demonstrates feasibility of the methodology, and should serve as the basis for a larger study of putative streptococcal-associated neuroimmunological disorders.