Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea

Kirvan, Christine A.; Swedo, Susan E.; Heuser, Janet S.; Cunningham, Madeleine W.

doi:10.1038/nm892

Cited by 420 publications

(446 citation statements)

References 42 publications

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“…However, a separate study identified a 60 kDa protein isolated from a neuroblastoma cell line and detected by TS patient sera as the human heat shock protein (hsp60) (Hoekstra et al, 2003). Finally, one study indicated that monoclonal antibodies derived from Sydenham's chorea patients recognized neurolipids and invoked Ca 2+ signaling cascades (Kirvan et al, 2003).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Crossreactivity has been found between N-acetyl-glucosamine (a streptococcal antigen) and lysoganglioside (a transmembrane molecule highly enriched in the CNS) using SC monoclonal antibodies. 146 However, it is still unclear how antibodies could cross the blood-brain barrier. The selective permeability of the blood-brain barrier presumably protects the brain from immunological insult.…”

Section: Environmental Factorsmentioning

confidence: 99%

Obsessive-compulsive disorder phenotypes: implications for genetic studies

et al. 2004

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Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes. Molecular Psychiatry (2005) 10, 258-275.

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“…M any disturbances in behavior, including paraneoplastic syndromes, movement disorders, schizophrenia, and autism, as well as other neuropsychiatric syndromes, have been associated with the presence of serum Abs with specificity for some, often unidentified, brain antigen (1)(2)(3)(4)(5)(6). Although data suggesting associations among disease states, brain-reactive Abs, and altered neuronal function continue to accumulate, there is no clear understanding of the mechanisms that permit serum Abs to gain access to brain tissue and then to mediate a change in behavior.…”

mentioning

confidence: 99%

Immunity and behavior: Antibodies alter emotion

Huerta

Kowal

DeGiorgio

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

258

226

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Systemic lupus erythematosus is an autoimmune disease in which most patients express Abs that bind double-stranded DNA. Recent work has shown that a subset of lupus Abs can crossreact with the NR2A and NR2B subunits of the NMDA receptor. This receptor is expressed in neurons throughout the brain but is at highest density within cells of the hippocampus, amygdala, and hypothalamus. The neurons in the CNS are normally protected from brain-reactive Abs by the blood-brain barrier (BBB); however, a breach in the barrier's integrity exposes neurons to potentially pathogenic Abs. Previously, we have shown that mice that are immunized with a peptide mimetope of DNA produce lupus-like Abs that crossreact with DNA and the NMDA receptor. Moreover, after abrogation of the BBB by treatment with lipopolysaccharide, the immunized mice display hippocampal neuron damage with ensuing memory impairment. Given that rises in epinephrine can increase cerebral blood flow and can cause leaks in the BBB, we decided to investigate whether epinephrine could act as a permissive agent for Ab-mediated neurotoxicity. Here, we show that peptide-immunized mice, given epinephrine to open the BBB, lose neurons in the lateral amygdala and develop a behavioral disorder characterized by a deficient response to fear-conditioning paradigms. Thus, the agent used to open the BBB determines which brain region is made vulnerable to neurotoxic Abs, and Abs that penetrate brain tissue can cause changes not only in cognitive competence, but also in emotional behavior.amygdala ͉ anti-NMDA receptor antibody ͉ anti-DNA antibody ͉ fear conditioning ͉ systemic lupus erythematosus

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Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea

Cited by 420 publications

References 42 publications

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

Obsessive-compulsive disorder phenotypes: implications for genetic studies

Immunity and behavior: Antibodies alter emotion

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