Group A streptococcus exposure and tic disorders in children: there’s a real link?

Introduction Following the description of a group of pediatric patients with Tourette’s syndrome in whom recrudescence of tics and worsening of behavioral features were associated to variations in the immunological response to Group A Streptococcus (the so called PANDAS infections), GAS exposure has figured as potential risk factors for developing a pediatric tic disorder. To this aim, the genetic population structure as well as the virulence traits of 187 non redundant GAS strains isolated from children with tic in the years 1996 - 2009 has been compared to that of GAS strains isolated from pediatric acute pharyngitis (465 strains from different surveys in the same years and geographic place) to investigate if enrichments of particular clones were present in the different GAS populations. Material and Methods Both GAS strains isolated from throat swabs of tic-affected children or acute pharyngitis cases were analysed by the emm typing method. The presence of superantigens speC gene, highly represented in GAS strains isolated from throat, was assessed by PCR. To verify a possible association between specific allelic speC forms and severity of clinical symptoms, the allelic variant of speC genes was assigned by speC amplicon sequencing and comparison with databank. Results During the study a wide range of emm types was observed. The most frequent type (emm12) did not exceed an overall incidence of 9.6% and 12.9 % in tic and pharyngitis GAS populations. Nevertheless, GAS strains isolated from the children presenting the most severe tics were enriched in particular serotypes and speC, in particular speC1 and speC2 alleles, while the same serotypes isolated from pharyngotonsillitis presented different speC alleles. Conclusions GAS strains possessing certain emm types and speC allelic variants are more represented in tic patients than in acute pharyngitis. These observations, however, represent a trend more than an evidence. A European project, the EMTICS project, has been funded by the FP7 Program to identify the genetic and environmental susceptibility factors of tic disorder. EMTICS hypotheses that the onset and/or exacerbation of tic and comorbid obsessive-compulsive disorders in children is associated with increased preceding occurrence of GAS exposure or infection as well as on host genetic susceptibility factors and mediated by immunological mechanisms. ISS is a partner involved in the characterization of GAS genetic population structure isolated from tic patients and controls. A more extensive description of the group A streptococcus genetic structure and virulence characteristics on a pan-European scale will give a more robust evidence on the real involvement of GAS and/or specific subpopulations in the pathology of pediatric tic disorders.