title: Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens.
abstract: The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen-dependent induction of autoantibodies in susceptible individuals may be involved the occurrence of tic disorders.
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bombaci
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
authors.forename: Marirosa
authors.initials: M
authors.lastname: Mora
authors.forename: Valerio
authors.initials: V
authors.lastname: Reguzzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Petracca
authors.forename: Eva
authors.initials: E
authors.lastname: Meoni
authors.forename: Sergio
authors.initials: S
authors.lastname: Balloni
authors.forename: Chiara
authors.initials: C
authors.lastname: Zingaretti
authors.forename: Fabiana
authors.initials: F
authors.lastname: Falugi
authors.forename: Andrea G O
authors.initials: AG
authors.lastname: Manetti
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.forename: Francesco
authors.initials: F
authors.lastname: Cardona
authors.forename: Graziella
authors.initials: G
authors.lastname: Orefici
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D006801:Humans; D010612:Pharyngitis / Q000097:blood / Q000276:immunology*; D040081:Protein Array Analysis; D013290:Streptococcal Infections / Q000097:blood / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D020323:Tics / Q000097:blood*
chemical_list: D000942:Antigens, Bacterial