Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study

Kawikova, Ivana; Leckman, James F.; Krönig, Holger; Katsovich, Lily; Bessen, Debra E.; Ghebremichael, Musie; Bothwell, Alfred L.M.

doi:10.1016/j.biopsych.2006.06.012

Cited by 99 publications

(68 citation statements)

References 47 publications

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“…It is also possible that there are age or medication effects that have yet to be discovered, and it is unclear what degree of overlap is present between the subgroup of TD patients identified as having altered cell-mediated immunity and the PANDAS cases. Indeed, the number of Tregs reported in the study by Kawikova et al (2007) was most pronounced in the non-PANDAS cases.…”

Section: Serologic and Prospective Studiesmentioning

confidence: 74%

“…Reduced numbers of Tregs are detected in autoimmune conditions including type 1 diabetes (Kukreja et al 2002), lupus erythematosus (Crispin et al 2003), rheumatoid arthritis (de Kleer et al 2004), and multiple sclerosis (Matarese et al 2005). Using flow cytometry techniques (Kawikova et al 2007), lower numbers of Tregs were found in the peripheral blood of 37 children with TD and/or OCD compared with healthy children. The reduction of Tregs was most noticeable in TD patients with higher disease severity or during symptom exacerbations.…”

Section: Serologic and Prospective Studiesmentioning

confidence: 99%

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The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Murphy

Kurlan

Leckman

2010

Journal of Child and Adolescent Psychopharmacology

143

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Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas-the basal ganglia of the brain and the related cortical and thalamic sites-adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS.

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Section: Serologic and Prospective Studiesmentioning

confidence: 74%

Section: Serologic and Prospective Studiesmentioning

confidence: 99%

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Murphy

Kurlan

Leckman

2010

Journal of Child and Adolescent Psychopharmacology

143

View full text Add to dashboard Cite

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“…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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“…A recent paper by Hornig noted that some patients with Tourette syndrome, OCD, and PANDAS show evidence of immune dysfunction [40]. Other studies show altered immunoglobulin profiles (IgM, IgG subclasses, IgA) and decreased levels of regulatory T-cells in PANS patients compared to healthy controls [41,42]. At the 2013 PANS Consensus Conference, it was recommended that PANS patients undergo immunodeficiency assessments [43].…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease of the Immune System: A New Variant of Immune Deficiency

Melamed¹

2016

Immunother Open Acc

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The interaction between infectious pathogens and the immune system has been a focus of research for many years. However, the failure of re-recognition or immune memory of infectious pathogen remains a clear mystery A memory B cell defect coupled with low levels of C1-INH and/or C1-INH function-failure of both the innate and adaptive immune components-may lead to persistent unresolved infection. Here we present 3 case studies that explore the abnormal immune response that may lead to persistent infection. These cases offer possible clarification of a longstanding clinical observation that some patients may develop a post infectious syndrome that includes various neurological symptoms and unusual fatigue. These patients may have positive serology seen only during acute infectious phase and have a documented positive PCR, suggesting active presence of the pathogen. The unusual presentation is prolonged and irreversible. We use the term "Alzheimer's disease of the immune system" to identify this subtype due to the memory defect of the immune system. As we identified 3 common immune defects in all cases, we suggest a new immune deficiency leading to the post infectious syndrome.

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Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study

Cited by 99 publications

References 47 publications

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Tourette syndrome and obsessive–compulsive disorder

Alzheimer’s Disease of the Immune System: A New Variant of Immune Deficiency

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