Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders

Morshed, Syed A.; Parveen, Salina; Leckman, James F.; Mercadante, Marcos T.; Kiss, Maria Augusta P. D.; Miguel, Eurí­pedes Constantino; Arman, Ayşe Rodopman; Yazgan, Yankı; Fujii, Tomoyuki; Paul, Surojit; Peterson, Bradley S.; Zhang, Heping; King, Robert A.; Scahill, Lawrence; Lombroso, Paul J.

doi:10.1016/s0006-3223(01)01096-4

Cited by 121 publications

(88 citation statements)

References 53 publications

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“…In contrast to several previous reports [39][40][41][42] and in agreement with others, [43][44][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: 88%

“…Third, because it has been postulated that GABHS infection must be the initial autoimmune response-inciting event but subsequent symptom exacerbations can be triggered by viruses, other bacteria, or noninfectious immunologic responses, 14 future studies will need to monitor patients systematically for other potential triggers. Much remains to be investigated in this area, including the potential roles of antineuronal antibodies, 41,43,44 bacterial superantigens, 59 host factors, and other regulators of immune responses, such as cytokines, chemokines, and specific subsets of T cells that have been implicated in autoimmune diseases. Additional prospective longitudinal studies are needed to clarify these mechanisms.…”

Section: Limitationsmentioning

confidence: 99%

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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: 88%

Section: Limitationsmentioning

confidence: 99%

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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“…However, this study and its important findings have yet to be replicated. A number of laboratories have examined serum from affected individuals and found evidence for autoantibodies [22][23][24][25]. Recent studies have also found evidence for the involvement of cytokines and regulatory T cells [26] [27].…”

Section: Pediatric Autoimmune Neuropsychiatric Disorder Associated Wimentioning

confidence: 99%

Tourette syndrome and obsessive–compulsive disorder

Lombroso

Scahill

2008

Brain and Development

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Tourette syndrome and obsessive-compulsive disorder are neuropsychiatric disorders that have sparked considerable interest over the decades. They are the focus of research for a remarkable diversity of disciplines, ranging from neuroimagers and prenatal epidemiologists to experts in the neural circuits that connect the cortex with the basal ganglia, as well as neuroimmunologists focusing on brain-based autoimmune phenomena. Several hypotheses have been put forward to explain the onset and exacerbation of these illnesses. Here we discuss the clinical phenomenology and treatment options that are currently available. New psychopharmacological agents are being used that are based on a greater understanding of the neurobiology and are being used in combination with behavioral interventions. Longitudinal clinical investigations into clinical symptoms and the natural course are providing additional clues on the underlying pathophysiology. Recent advances in research models are also reviewed in an attempt to clarify some of the molecular etiologies that lead to these disorders. KeywordsTorrette syndrome; obsessive-compulsive disorder; basal ganglia; autoimmune disorders; streptococcal infections; neuroleptic treatment Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are model neuropsychiatric disorders that have been the subject of medical interest for centuries [1]. Many explanations have been suggested for the etiology of tics and OCD symptoms and have included genetic factors, the influence of toxins, psychological, and infectious processes. There have been significant advances of our understanding of the neurobiological mechanisms at work in these disorders, as well as improvements in the treatments available. Several reviews on more specialized aspect of TS, OCD and related disorders have appeared over the last several years [2][3][4]. Here we concentrate on the clinical features of tic disorders and OCD and discuss evidence-based interventions for these disorders. Tourette syndromeTourette syndrome is one of several tic disorders that are classified either by their type (motor or phonic tic) or their duration (transient or chronic). The diagnosis of a transient tic is made if the tics are present for less than 12 months. If the tics persist for more than 12 months, they

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“…Previous studies have proposed that antineural antibodies in patients with tic disorders and related conditions, such as obsessive-compulsive disorder [1][2][3][4][5][6][7]. Swedo and colleagues proposed the existence of a group of patients with pediatric antoimmune neuropsychiatric disorders associated with streptococcal infection, or ''PANDAS'' [8].…”

Section: Introductionmentioning

confidence: 99%

Antineural antibody in patients with Tourette’s syndrome and their family members

Yeh

Wu²,

Tsung³

et al. 2005

J Biomed Sci

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SummaryIt has been proposed that antineural antibodies were present in patients with Tourette's syndrome (TS) and other neuropsychiatric disorders. The purpose of our study was to investigate the presence of antineural antibodies in the individuals with Tourette's syndrome and the family members of TS patients. The sera of four TS patients with no current streptococcal infection, their tic-free family members including father, mother and sibling, and a age-matched control group who were tic free were assayed for antineural antibodies directed against rat tissue and neurons in primary cell culture. There were prominent antineural antibodies present in TS patients and their first-degree family members, but not in the control group. Western blotting showed proteins of about 120 kDa in their sera that were not present in the sera of controls. The preliminary results of our study suggest the importance of genetic vulnerability in the immunological pathophysiology of tic disorders. Future studies should investigate the interactions of genetics, environment, infectious agents, and immunity on symptom expression in families with tic disorders.

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Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders

Cited by 121 publications

References 53 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

Tourette syndrome and obsessive–compulsive disorder

Antineural antibody in patients with Tourette’s syndrome and their family members

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