Oxidative stress and gut-derived lipopolysaccharides in children affected by Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.
Abstract Backgroundpaediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to assess NOX2 activity, as well as serum 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut of patients with PANDAS. Methodsa cross sectional study was performed to compare serum activity of soluble NOX-2-dp (sNOX-2-dp), blood levels of isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used to assess gut permeability. Resultscompared with CT, PANDAS children had higher values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). LPS significantly correlated with serum zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Isoprostanes and zonulin emerged as the only independent predictive variables associated with sNOX2-dp (R2=68%).Conclusionthis study provides the first report attesting that children affected by PANDAS have high NOX2 activation, oxidative stress and circulating levels of LPS that could be potentially implicated in the process of neuroinflammation.