An Investigation of the Levels of Serine Protease and Associated Molecules in Children with Autism Spectrum Disorder

Abstract

This study aimed to elucidate the potential role of serine proteases and their associated regulatory molecules in the etiopathogenesis of autism spectrum disorder (ASD) and to assess their relationship with symptom severity and specific behavioral domains in children diagnosed with ASD. A cross-sectional design was employed, including 44 children aged 2 to 6 years with a confirmed diagnosis of ASD and 43 age- and sex-matched typically developing children as controls. Behavioral assessments were conducted using the Childhood Autism Rating Scale (CARS), the Autism Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised, Turkish Version (RBS-R-TV). Serum concentrations of motopsin, agrin, C-terminal agrin fragment (CAF), tissue plasminogen activator (tPA), neuroserpin, and plasminogen activator inhibitor-1 (PAI-1) were determined using enzyme-linked immunosorbent assay (ELISA). Serum levels of all analyzed molecules were significantly reduced in the ASD group compared to controls (p < 0.05 for all). Although no significant associations were observed between total ASD severity scores and biomarker concentrations, notable correlations emerged between specific behavioral subdomains and select biomarkers. Motopsin levels exhibited a moderate positive correlation with the “imitation” subdomain of CARS and the “sensory” subdomain of ABC. Conversely, agrin levels demonstrated moderate inverse correlations with “listening response,” “taste–smell-touch response and use,” and “activity level” subdomains of CARS. PAI-1 levels showed a significant negative correlation with the “self-injurious behavior” subdomain of RBS-R-TV. The findings suggest that serine proteases and their modulators implicated in synaptic remodeling and neuroplasticity may contribute to the underlying neurobiological mechanisms of ASD. The observed domain-specific associations support the hypothesis that ASD comprises heterogeneous neurodevelopmental trajectories, and that peripheral biochemical markers reflecting these pathways may aid in the identification of ASD subtypes and guide personalized therapeutic strategies.