Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity.

The American Journal of Psychiatry
Jian XuChristopher Pittenger

Abstract

Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, describes such a situation after infection with Streptococcus pyogenes. PANDAS may result from induced autoimmunity against brain antigens, although this remains unproven. Pilot work suggests that IgG antibodies from children with PANDAS bind to cholinergic interneurons (CINs) in the striatum. CIN deficiency has been independently associated with tics in humans and with repetitive behavioral pathology in mice, making it a plausible locus of pathology. The authors sought to replicate and extend earlier work and to investigate the cellular effects of PANDAS antibodies on cholinergic interneurons. Binding of IgG to specific neurons in human and mouse brain slices was evaluated ex vivo after incubation with serum from 27 children with rigorously characterized PANDAS, both at baseline and after intravenous immunoglobulin (IVIG) treatment, and 23 matched control subjects. Binding was correlated with symptom measures. Neural activity after serum incubation was assessed in mouse slices using molecular markers and electrophy...Continue Reading

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Citations

Jan 2, 2021·The American Journal of Psychiatry·Ned H Kalin
Jan 2, 2021·The American Journal of Psychiatry·Wayne K GoodmanSameer A Sheth
Jan 2, 2021·The American Journal of Psychiatry·Steven E Hyman
Jun 15, 2021·Frontiers in Neuroscience·Federica MurgiaAlessandro Zuddas

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Methods Mentioned

BETA
ELISA
dot blot
fluorescence imaging
transgenic

Clinical Trials Mentioned

NCT01281969

Software Mentioned

SPSS Statistics
Fiji ImageJ
Prism
Clampfit

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