title: Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Cox
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D002819:Chorea / Q000276:immunology* / Q000523:psychology; D006801:Humans; D009069:Movement Disorders / Q000276:immunology* / Q000523:psychology*; D011954:Receptors, Dopamine / Q000276:immunology / Q000378:metabolism*; D013290:Streptococcal Infections / Q000276:immunology
chemical_list: D001323:Autoantibodies; D011954:Receptors, Dopamine
keywords: autoimmunity; chorea; dopamine; dopamine receptor; streptococci