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

SUMMARY

“Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity” provides compelling evidence that immunoglobulin G (IgG) antibodies from children diagnosed with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) selectively bind to striatal cholinergic interneurons (CINs) in both human and mouse brain tissue.

The study found that antibodies from children with PANDAS disrupted CIN function, as evidenced by decreased molecular and electrical activity. Importantly, this effect was not seen in other types of interneurons or in samples from control subjects.

Serum from PANDAS patients post-treatment with intravenous immunoglobulin (IVIG) showed reduced CIN binding and restored activity levels, correlating with clinical improvement in OCD symptoms. The study confirms that CINs are specifically targeted by antibodies in three separate groups of children with PANDAS and strengthens these findings by demonstrating functional effects using ex vivo electrophysiological tests. These results not only validate CINs as a potential cellular locus for symptom generation in PANDAS but also strengthen the hypothesis of an autoimmune mechanism, possibly via molecular mimicry. The work suggests a biomarker for diagnosis and supports the rationale for immunomodulatory treatment.

LINK TO PAPER: https://doi.org/10.1176/appi.ajp.2020.19070698