Journal Article

Oxidative Stress and Low-Grade Endotoxemia in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Insights from a Cross-Sectional Study

Iantorno, Laura, Brindisi, Giulia, Aloisio, Simone, Malvasi, Mariaelena, Capponi, Martina, Guido, Cristiana Alessia, Forte, Maurizio, Violi, Francesco, Pignatelli, Pasquale, Loffredo, Lorenzo, Baratta, Francesco, Carnevale, Roberto, Pacella, Elena, Picchio, Vittorio, Spalice, Alberto, Totè, Chiara Maria, Salvatori, Francesca, Bartimoccia, Simona, Zicari, Anna Maria

2025

Overview

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R2 = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits.

• Publisher: MDPI AG
• Subject: Adolescent / Alzheimer's disease / Autism / Autoimmune Diseases - blood / Autoimmune Diseases - metabolism / Biomarkers - blood / Brain research / Child / Child, Preschool / Cross-Sectional Studies / Disease / Endotoxemia - blood / Endotoxemia - etiology / Endotoxemia - metabolism / Enzymes / Female / Gut microbiota / Haptoglobins - metabolism / Humans / Infections / Inflammation / Isoprostanes - blood / Lipopolysaccharides - blood / Male / Mental Disorders / Metabolism / Metabolites / Microbiota / NADPH Oxidase 2 - blood / Nervous system / Obsessive compulsive disorder / Oxidative Stress / Pediatrics / Permeability / Probiotics / Protein Precursors - blood / Regression analysis / Streptococcal Infections - blood / Streptococcal Infections - complications / Streptococcal Infections - metabolism