Identification of Serum Proteome in Children with Autism Spectrum Disorder

Abstract Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and restricted, repetitive behaviors. Early and accurate diagnosis is essential for timely intervention and improved outcomes. While numerous efforts have been made to identify reliable biomarkers, no clinically validated protein biomarkers for ASD are currently available. The identification of such biomarkers could aid in diagnosis, subtyping, treatment monitoring, and the discovery of novel therapeutic targets. In this study, we analyzed the serum proteome profiles of children with ASD compared to typically developing children (TDC) using an iTRAQ-based quantitative proteomic approach. Pooled serum samples were assessed to identify potential ASD-associated protein biomarkers. A total of 59 differentially expressed proteins were identified between the ASD and TDC groups. These proteins are implicated in several biological pathways, including cholesterol metabolism, complement and coagulation cascades, tight junctions, regulation of the actin cytoskeleton, and extracellular matrix (ECM)-receptor interactions. Notably, levels of complement C4A, APOC2, and PFN1 were significantly elevated in the ASD group, while proteins involved in ECM-cell interactions - HSPG2, HPSE, and NID1 - were markedly decreased. These findings highlight a distinct proteomic signature in ASD and suggest that the identified proteins may serve as promising candidates for molecular biomarkers. Further validation in larger, independent cohorts is warranted to establish their diagnostic and clinical utility.