Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder

Cox, Carol J.; Zuccolo, Amir; Edwards, Erica; Mascaro-Blanco, Adita; Alvarez, Kathy; Stoner, Julie A.; Chang, Kiki; Cunningham, Madeleine W.

doi:10.1089/cap.2014.0048

Cited by 80 publications

(76 citation statements)

References 47 publications

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“…In our study of over 260 children, sera IgG from chronic OCD, tics or both reacted significantly with human D1 receptor or lysoganglioside antigens and had significantly elevated CaMKII activation compared with normal controls (Cox et al . ). Chronic tics and OCD did not react above normal levels with D2L receptor (Cox et al .…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 97%

“…We investigated further the possibility that dopamine receptors such as the D1 and D2 receptors may be involved in disease (Cox et al . , ). Studies using the membrane antigen targets in an ELISA as well as dopamine receptor signalling assays in transfected cell lines and FLAG‐tagged epitopes on the D2 dopamine receptor all confirmed the reaction of mAb 24.3.1, and IgG from chorea serum and CSF additionally confirmed reactivity with the D2 dopamine receptor (Cox et al .…”

Section: Sydenham Chorea‐derived Human Mabsmentioning

confidence: 99%

“…In the second group with chronic tics and/or OCD, antibodies may be abnormally elevated against D1R and/or lysoganglioside antigens (Cox et al . , Singer et al . ).…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

“…Chronic tics and OCD did not react above normal levels with D2L receptor (Cox et al . , Singer et al . ).…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

“…In our group of over 260 youth and young adults, chronic OCD and/or tics was positively associated with streptococcal infection status (Cox et al . ) and with autoantibodies against neuronal antigens, D1R and lysoganglioside. The antibody‐mediated neuronal cell signalling of CaMKII activation in human neuronal cells in these diseases suggests that the antibodies may target the receptors and alter dopamine neurotransmission leading to neuropsychiatric symptoms.…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

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Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond

Cunningham

Cox

2015

Acta Physiologica

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Antineuronal autoantibodies are associated with the involuntary movement disorder Sydenham chorea (SC) and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) which are characterized by the acute onset of tics and/or obsessive compulsive disorder (OCD). In SC and PANDAS, autoantibodies signal human neuronal cells and activate calcium calmodulin-dependent protein kinase II (CaMKII). Animal models immunized with group A streptococcal antigens demonstrate autoantibodies against dopamine receptors and concomitantly altered behaviours. Human monoclonal antibodies (mAbs) derived from SC target and signal the dopamine D2L (long) receptor (D2R). Antibodies against D2R were elevated over normal levels in SC and acute-onset PANDAS with small choreiform movements, but were not elevated over normal levels in PANDAS-like chronic tics and OCD. The expression of human SC-derived anti-D2R autoantibody V gene in B cells and serum of transgenic mice demonstrated that the human autoantibody targets dopaminergic neurones in the basal ganglia and other types of neurones in the cortex. Here, we review current evidence supporting the hypothesis that antineuronal antibodies, specifically against dopamine receptors, follow streptococcal exposures and may target dopamine receptors and alter central dopamine pathways leading to movement and neuropsychiatric disorders.

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Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 97%

Section: Sydenham Chorea‐derived Human Mabsmentioning

confidence: 99%

“…In the second group with chronic tics and/or OCD, antibodies may be abnormally elevated against D1R and/or lysoganglioside antigens (Cox et al . , Singer et al . ).…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

“…Chronic tics and OCD did not react above normal levels with D2L receptor (Cox et al . , Singer et al . ).…”

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

Section: Anti‐dopamine Receptor Autoantibodies In Sydenham Chorea Pamentioning

confidence: 99%

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Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond

Cunningham

Cox

2015

Acta Physiologica

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Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae

Rafeek

Lobbe

Wilkinson

et al. 2021

Anim Models and Exp Med

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Background The neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS). Methods Standard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive‐compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens. Results For control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age‐dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively. Conclusion We have characterised a new model that provides longitudinal stability of age‐dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post‐streptococcal complications.

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Inflammation in obsessive–compulsive disorder: A literature review and hypothesis‐based potential of transcranial photobiomodulation

Coelho,

Salvi,

Vieira

et al. 2024

J of Neuroscience Research

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Obsessive–compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%–3% of the global population. Despite the availability of several treatments, many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobiomodulation (t‐PBM) with near‐infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T‐cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflammatory cytokines such as TNF‐α, CRP, IL‐1β, and IL‐6. We also examined the hypothesis‐based potential of t‐PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t‐PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on randomized clinical trials to assess t‐PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t‐PBM sessions.

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Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder

Cited by 80 publications

References 47 publications

Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond

Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond

Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae

Inflammation in obsessive–compulsive disorder: A literature review and hypothesis‐based potential of transcranial photobiomodulation

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