Pediatric Neuroimmune and Inflammatory Overlap: Immunopathology of PANS/PANDAS in Autism Spectrum Disorder

Abstract

This article, the fourth in the neuroimmune series, examines immunopathologic features of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and PANDAS in children with autism spectrum disorder (ASD), emphasizing potential mechanisms by which Chronic Inflammatory Response Syndrome (CIRS) may trigger or amplify neuroimmune dysregulation. Findings indicate a restricted set of HLA DR-DQ haplotypes, reduced α-melanocyte-stimulating hormone (MSH), and elevated cytokines including TGF-β1, MMP-9, and C4a, reflecting multi-system immune dysregulation. Symptom profiles spanned obsessive-compulsive behaviors, anxiety, rage reactions, disordered eating, and non-Tourette’s tics, often overlapping with core ASD features. Neuroimaging and transcriptomic profiling in subsets of cases revealed structural and molecular alterations consistent with hypometabolic neuroimmune states. These results highlight PANS/PANDAS as complex, multi-system neuroimmune disorders, with CIRS-related mechanisms potentially amplifying clinical expression.

Key Biomarkers

Symptom Clusters