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Laboratory Studies of Cross-Reactive (Anti-Gas/Anti-Brain) Antibodies in Sydenham’s Chorea and PANDAS/PANS

Reference
[Frick2018]
Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum
Luciana R. Frick, Maximiliano Rapanelli, Kantiya Jindachomthong, Paul Grant, James F. Leckman, Susan Swedo, Kyle Williams, Christopher Pittenger, Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum, Brain, Behavior, and Immunity, Available online 9 December 2017, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2017.12.004.

Reference
[Nicolini2015]
Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.
Humberto Nicolini, Yaumara López, Alma D. Genis-Mendoza, Viana Manrique, Lilia Lopez-Canovas, Esperanza Niubo, Lázaro Hernández, María A. Bobes, Ana M. Riverón, Mavil López-Casamichana, et al.
Actas Esp Psiquiatr. 2015 Mar-Apr; 43(2): 35–41. Published online 2015 Mar 1.

Reference
[Cox2015]
Cox CJ, Zuccolo AJ, Edwards EV, et al. Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):76-85. doi:10.1089/cap.2014.0048.

Reference
[Kirvan2007]

Finding/Critique
Tubulin is a neuronal target of autoantibodies in Sydenham’s chorea
Findings: (N=1, C=1) Monoclonal antibody 23.1.1 is isolated from patient with Sydenham chorea and is shown to bind with Tubulin and drive CaM Kinase II activation.

Critique: none known

Reference
[Kirvan2006]

Finding/Critique
Antibody-mediated neuronal cell signaling in behavior and movement disorders.
Findings: (N=23, C=26) Sera from acute PANDAS patient (16) and Sydenham’s chorea patients (7)are compared to non-PANDAS controls (OCD, Tics, ADHC). Results indicate significant separation based on CaM Kinase II activation.

Critique: Significant finding. Recommendation for repeat to ensure repeatable methodology.

Reference
[Singer2004]

Finding/Critique
Anti-basal ganglia antibodies in PANDAS
Findings: (N=14, C=14) Antibodies were isolated from 14 children that met the PANDAS criteria. Key findings were mean binding to epitope at 183 kDA. Competitive ELISA did not significantly separate subjects from controls.

Critique: Small sample size, selection of controls unclear. Unclear if subjects were in acute exacerbation or in convalescence.

Reference
[Singer2003]

Finding/Critique
Anti-basal ganglia antibody abnormalities in Sydenham chorea.
Findings: (N=9, C=9) Antibodies were isolated from 9 children with SC and compared to controls. Key findings were molecular masses at 126 and 113 kDa on Western Blot. Competitive ELISA did not significantly separate subjects from controls.

Critique: Small sample size and selection of controls unclear

Reference
[Kirvan2003]

Finding/Critique
Mimicry and Autoantibody-Mediated Neuronal Cell Signaling in Sydenham Chorea
Findings: (N=1)Authors isolate three monoclonal antibodies in chorea sera that activate cell signaling (CaM Kinase II) in human neuronal cells. Convalescent sera and sera from non-SC controls did not activate cell signaling. The monoclonal antibodies have high affinity for the dominant epitope of GABHS carbohydrate implicating these cross-reactive antibodies in the immunopathegenesis of Sydenham chorea.

Critique: Extremely significant finding and in need of replication.

Reference
[Harel2001]

Finding/Critique
Antibodies against human putamen in adolescents with anorexia nervosa.
Findings: (N=22, C=22) Antiputamen antibodies are found in adolescents with active anorexia nervosa. Author concludes that issues in underlying immune process at putamen level may exist for some patients with eating disorder.

Critique: Relationship of the anti-putamen antibodies to GABHS is unclear.

Reference
[Husby1976]

Finding/Critique
Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever.
Findings: (N=30 SC, N=50 ARF/non-SC, C=55) 46% of sera from 30 children with rheumatic chorea showed IgG antibody reacting with neuronal cytoplasm of human caudate and subthalamic nuclei. This reaction was also noted in 14% of 50 children with rheumatic carditis without chorea. Controls had no/low amounts of antibody. In rheumatic chorea, anti-neuronal antibody appeared to cross-react with antigens shared by Group A streptococcal membranes.

Critique: non-noted, relatively older study.