An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection. In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls. ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus. ELISA optical density values did not differ between PANDAS patients and controls across all preparations. Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density. Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination. Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups. In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder. Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics.

Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies. We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation. The effect of antibodies against the streptococcal M5 protein were also studied. A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls). Cannulas were placed bilaterally and symmetrically by stereotactic techniques. After animals were allowed to recover for 1 week, sera were microinfused for 3 days. Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion. No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups. Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders.

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