PANDAS: Too Narrow a View of the Neuroimmune Landscape

Hyman discusses the study of Xu et al wherein they advance the argument for the validity of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) by reporting that IgG antibodies from the serum of children who meet criteria for PANDAS bind to cholinergic interneurons (CINs) but not to other interneuron cell types within the striatum (a component of the basal ganglia). The authors had previously shown that targeted ablation of CINs in mouse striatum results in tic-like stereotypies, but it must be recognized that diverse genetic and pharmacologic manipulations of the basal ganglia have been shown to produce obsessive-compulsive disorder (OCD)-like symptoms. Xu et al endeavor to demonstrate an immunologic mechanism for PANDAS. Their study design is complex, perhaps necessitated by a paucity of rigorously diagnosed PANDAS patients in research settings.