Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity.
Level 4 - case-series / case-control
Case-control study with ex vivo translational assays using human patient sera
PubMed 32539528 · doi:10.1176/appi.ajp.2020.19070698
What was done
Serum IgG binding to specific neurons was assessed ex vivo in human and mouse brain slices using serum from 27 children with rigorously characterized PANDAS (at baseline and after intravenous immunoglobulin [IVIG] treatment) and 23 matched control subjects across three independent cohorts. The investigators correlated binding levels with symptom measures and examined neural activity and electrophysiology in acute mouse brain slices exposed to patient serum.
What was found
IgG from children with PANDAS bound to striatal cholinergic interneurons (CINs), but not to several other neuron types, significantly more than IgG from control subjects (no specific binding percentages or numerical values reported in the abstract). Post-IVIG serum showed reduced CIN binding that correlated with symptom improvement. Baseline PANDAS sera decreased striatal CIN activity and altered electrophysiological responses in mouse brain slices without altering parvalbumin-expressing GABAergic interneurons, whereas post-IVIG sera and IgG-depleted baseline sera did not alter CIN activity.
Why it matters
This study identifies striatal cholinergic interneurons as a specific cellular target of autoantibodies in PANDAS, providing a mechanistic link between post-streptococcal autoimmunity and rapid-onset obsessive-compulsive symptoms.
Limits
The abstract reports no numerical values, effect sizes, or confidence intervals. The sample size is modest (27 cases, 23 controls), and functional electrophysiological measurements were conducted ex vivo in mouse tissue rather than in vivo.
Cited by
- supports Streptococcal infections in children can trigger pediatric autoimmune neuropsychiatric disorders (PANDAS) affecting the basal ganglia and caudate nucleus, causing OCD symptoms.