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Sonbol, H.M., Abdelmawgoud, A.S., El-kady, N.M. et al. Serum zonulin level in autistic children and its relation to severity of symptoms a case-control study. Sci Rep 15, 27802 (2025). https://doi.org/10.1038/s41598-025-11420-0

• Findings: Children with autism had significantly higher serum zonulin levels (avg. 73 ng/ml) vs. neurotypical controls (avg. 22 ng/ml).
• Correlation: Higher zonulin levels were strongly associated with greater symptom severity (r = 0.9).
• Mechanism: Zonulin regulates tight junctions in the intestinal and blood–brain barriers; elevated levels increase permeability (“leaky gut”), promoting systemic and neuroinflammation.
• Relevance to PANS/PANDAS: Similar barrier dysfunction and inflammation may contribute to symptom flares following infections or immune triggers.

Han VX, Alshammery S, Keating BA, Gloss BS, Hofer MJ, Graham ME, Aryamanesh N, Marshall LL, Yuan S, Maple-Brown E, Yan J, Bandodkar S, Kothur K, Nishida H, Jones H, Tsang E, Lau X, Dissanayake R, Perkes I, Mohammad SS, Brilot F, Gold W, Patel S, Dale RC, et al. Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome. Molecular Psychiatry. 2025;30:5389–5404. doi:10.1038/s41380-025-03127-5

• Compared children with PANS and other neurodevelopmental disorders to neurotypical controls; PANS/non-PANS groups reported more early childhood infections and loss of previously acquired developmental skills than controls.

• Found routine immune testing largely normal, but RNA sequencing showed upregulated ribosomal biogenesis/RNA methyltransferase pathways and downregulated mitochondrial, signaling, endocytosis, and immune pathways.

• Toll-like receptor stimulation showed reduced TNF and IL-6 responses in PANS; post-IVIG RNA sequencing demonstrated partial normalization of dysregulated pathways.

• Authors conclude findings support immune and epigenetic dysregulation in PANS and provide rationale for immune-modulating therapies.