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. 2025 Jul 1;26(13):6336.
doi: 10.3390/ijms26136336.

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

Chiara Maria Totè  1 , Martina Capponi  2 , Francesca Salvatori  2 , Anna Maria Zicari  2 , Cristiana Alessia Guido  2 , Giulia Brindisi  2 , Laura Iantorno  1 , Simona Bartimoccia  3 , Francesco Baratta  1 , Maurizio Forte  4 , Vittorio Picchio  4 , Mariaelena Malvasi  5 , Simone Aloisio  6 , Elena Pacella  5 , Pasquale Pignatelli  1 , Francesco Violi  1   4 , Roberto Carnevale  3   4 , Alberto Spalice  2 , Lorenzo Loffredo  1
Affiliations

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

Chiara Maria Totè et al. Int J Mol Sci. .

Abstract

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.

Keywords: LPS; NADPH oxidase; NOX2; PANDAS; PANS; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Box whisker plots of sNOX2-dp (A), serum isoprostanes (B), LPS (C), and zonulin (D) in controls, PANDAS and PANS. The controls are shown in blue, the PANDAS in yellow, and the PANS in red. * The asterisks indicate a comparison with the significant p.
Figure 2
Figure 2
Linear correlation analysis between levels of sNOX2-dp with serum isoprostanes (A), LPS (B), and zonulin (C).
Figure 3
Figure 3
In children with PANDAS, unlike those with PANS, the increase in low levels of endotoxemia could, through binding to TLR4, activate NOX2. This, in turn, might lead to increased oxidative stress at both the systemic and cerebral levels, promoting neuroinflammation.
See this image and copyright information in PMC

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