Increased titers of antibodies against streptococcal M12 and M19 proteins in patients with Tourette's syndrome

Müller, Norbert; Kroll, Bernd; Schwarz, Markus J.; Riedel, Michael; Straube, Andreas; Lütticken, Rudolf; Reinert, Ralf René; Reineke, Thorsten; Kühnemund, O

doi:10.1016/s0165-1781(01)00215-3

Cited by 59 publications

(35 citation statements)

References 25 publications

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“…In contrast to several previous reports [39][40][41][42] and in agreement with others, 43-45 we did not find that our patients had higher titers of antistreptococcal antibodies. The reason for these discrepancies is unclear but is possibly related to regional and seasonal differences and the composition of the patient sample.…”

Section: Subjectssupporting

confidence: 87%

Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections

Luo¹,

et al. 2004

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ABSTRACT. Background. It has been proposed that infection by group A ␤-hemolytic streptococci (GABHS) can trigger acute symptom exacerbations among patients with Tourette's syndrome (TS) or obsessive-compulsive disorder (OCD), via autoimmune mechanisms.Objective. To examine the temporal relationship between newly acquired GABHS infections (and other immunologic indices) and acute exacerbations of tics and obsessive-compulsive symptoms.Methods. Pediatric patients (7-17 years of age) with TS and/or OCD (N ‫؍‬ 47) and healthy control subjects (N ‫؍‬ 19) were prospectively monitored for newly acquired GABHS infections, nonspecific markers of acute inflammatory responses, and D8/17-reactive cells (a marker of rheumatic fever). Objective monthly ratings of tic and obsessive-compulsive symptom severity were used to determine the timing of symptom exacerbations.Results. The overall rate of acute exacerbations of neuropsychiatric symptoms was 0.56 exacerbations per patient per year. The average rate of new GABHS infections, using a stringent definition, was 0.42 infections per subject per year among patients, compared with 0.28 infections per subject per year for control subjects. The association between symptom exacerbations and new GABHS infections among patients was no greater than that expected on the basis of chance. At baseline, patients demonstrated significantly higher levels of D8/17-reactive cells and neopterin, compared with control subjects, but there was no consistent pattern of change when exacerbation time points were compared with baseline or follow-up time points.Conclusions. The results suggest no clear relationship between new GABHS infections and symptom exacerbations in an unselected group of patients with TS and/or OCD. Pediatrics 2004;113:e578 -e585. URL: http://www. pediatrics.org/cgi/content/full/113/6/e578; Tourette's syndrome, obsessive-compulsive disorder, PANDAS, group A ␤-hemolytic streptococci, D8/17, neopterin, C-reactive protein.ABBREVIATIONS. ADHD, attention-deficit/hyperactivity disorder; ASO, anti-streptolysin O; BRR, B repeat region; CRP, C-reactive protein; CRR, C repeat region; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale; GABHS, group A ␤-hemolytic streptococci; OCD, obsessive-compulsive disorder; OC, obsessive compulsive; PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; RF, rheumatic fever; TS, Tourette's syndrome; YGTSS, Yale Global Tic Severity Scale; IgG, immunoglobulin G.T ic disorders, obsessive-compulsive disorder (OCD), and related conditions affect as many as 3% of children and adolescents. [1][2][3][4][5][6] The factors that contribute to the pathogenesis of these disorders are poorly defined. The hypothesis that infections can modulate the clinical appearance of tic disorders dates from the 1800s. 7 The past decade has seen the reemergence of the hypothesis that postinfectious immune mechanisms account for at least some cases of Tourette's syndrome (TS) and OCD.It is well known that group A ␤-hemolytic streptococci (GABHS...

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Section: Subjectssupporting

confidence: 87%

Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections

Luo¹,

et al. 2004

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“…Interestingly, the strongest reactivity was detected with the extracellular proteins of the pathogenic strain MGAS315. In agreement with these findings, it has previously been shown that TS patients have increased titers against M12 and M19 proteins (Müller et al, 2001). While PK was not selectively detected, glycolytic enzymes have been shown to either occur on the surface of streptococci or be secreted and contribute to pathogenesis (Fontân et al, 2000).…”

Section: Immunoreactivity Between Pk and The Streptococcal M Proteinssupporting

confidence: 65%

“…For example, one study using an administrative regional database of more than 500,000 privately insured individuals linked recent GABHS infections with an increased risk of tic disorders and OCD (Mell et al, 2005). Another study reported that over 90% of TS patients that tested positive for anti-basal ganglia antibodies had serological evidence of a recent streptococcal infection (Church et al, 2003), and two other studies showed that TS patients' sera possessed elevated streptococcal antibody titers (Müller et al, 2001;Müller et al, 2000). However, these results have not been confirmed by other reports (Loiselle et al, 2003;Luo et al, 2004;Morshed et al, 2001;Singer et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

Kansy

Katsovich

McIver

et al. 2006

Journal of Neuroimmunology

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Immune responses to β-hemolytic streptococcal infections are hypothesized to trigger tic disorders and early-onset obsessive-compulsive disorder (OCD) in some pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme, pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated disorders. Antibodies to PK reacted strongly with surface antigens of infectious strains of streptococcus, and antibodies to streptococcal M proteins reacted with PK. Moreover, immunoreactivity to PK in patients with exacerbated symptoms who had recently acquired a streptococcal infection was 7-fold higher compared to patients with exacerbated symptoms and no evidence of a streptococcal infection. These data suggest that PK can function as an autoimmune target and that this immunoreactivity may be associated with Tourette syndrome, OCD, and associated disorders.

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“…Evidências indiretas sugerem que as proteínas M12 e M19 possuem receptores semelhantes a determinadas estruturas cerebrais 15 bem como tecidos periféricos. Müller et al 15 realizou um estudo correlacionando os diferentes subtipos de proteína M em casos de Síndrome de Tourette secundários a infecções estreptocócicas.…”

Section: Fonte: Adaptado Livremente De Swedo Et Al³unclassified

“…Müller et al 15 realizou um estudo correlacionando os diferentes subtipos de proteína M em casos de Síndrome de Tourette secundários a infecções estreptocócicas. Constatou-se altos títulos de ASLOanti-estreptolisina O -definindo a infecção primária, assim como elevados títulos para anticorpos anti M12 e M19.…”

Section: Fonte: Adaptado Livremente De Swedo Et Al³unclassified

A hipótese imunológica no Transtorno Obsessivo-Compulsivo: revisão de um subtipo (PANDAS) com manifestação na infância

Ronchetti

Böhme

Ferrão

2004

Rev. psiquiatr. Rio Gd. Sul

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INTRODUÇÃOO Transtorno Obsessivo-Compulsivo (TOC) é um transtorno que atinge cerca de 2,5% de indivíduos na população geral¹. A sintomatologia característica do TOC também se faz presente em outras situações, em especial nos demais Transtornos do espectro ObsessivoCompulsivo, como a Síndrome de Tourette (ST). Apesar da prevalência e dos altos custos anuais decorrentes dos transtornos citados, pouco se sabe acerca de sua etiologia. Aceita-se, atualmente, a ocorrência de herança multifatorial nos indivíduos portadores, ou seja, uma herança genética associada à resposta do indivíduo a estressores ambientais². Entretanto, ainda não foi identificada a carga genética específica para pacientes suscetíveis ao TOC e demais transtornos associados. Postula-se, portanto, a importância dos estressores ou fatores de risco para o desenvolvimento de tais patologias.Uma das mais recentes teorias, envolvendo fatores de risco associados ao TOC, correlaciona a ocorrência de infecção estreptocócica precedendo quadro, por vezes transitório, de TOC e Transtornos de Tique (como ST) em crianças. Mesmo em se tratando de uma constatação recente, aplicável apenas a um quadro específico³ (sintomas subitamente estabelecidos ou exacerbação dramática de sintomatologia pré-existente), a "hipótese imunológica" pode representar um avanço no entendimento da fisiopatologia do TOC, bem como no seu tratamento.Partindo do modelo já conhecido da Coréia de Sydenham pós-febre reumática, assim como do quadro clínico, das alterações imunes e de neuroimagem observadas no TOC, foi proposto um subgrupo de TOC em crianças denominado PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococal infections). Tal entidade não apenas define um fator de risco específico (infecção primária por estreptococo B-hemolítico do grupo A) como também promove a discussão sobre diagnósti-co diferencial e tratamento -uma vez se tratan-

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Increased titers of antibodies against streptococcal M12 and M19 proteins in patients with Tourette's syndrome

Cited by 59 publications

References 25 publications

Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections

Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

A hipótese imunológica no Transtorno Obsessivo-Compulsivo: revisão de um subtipo (PANDAS) com manifestação na infância

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