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

Researchers studied blood levels of six proteins involved in brain development in 87 young children (44 with autism, 43 without). All six proteins were lower in children with autism. Interestingly, some proteins related to specific autism behaviors - for example, one protein was linked to imitation skills and sensory issues, while another related to self-harm behaviors. This suggests autism may have different biological subtypes and that blood tests might eventually help identify these differences.

This cross-sectional study examined serine protease levels in 44 children with ASD (ages 2-6) compared to 43 typically developing controls. Researchers measured six biomarkers involved in brain development and synaptic function using blood tests. All measured molecules were significantly lower in children with ASD. While total autism severity scores didn't correlate with biomarker levels, specific behavioral domains showed notable associations: motopsin correlated with imitation and sensory behaviors, agrin with listening and sensory responses, and PAI-1 with self-injurious behaviors.

The findings suggest these molecules, which help regulate brain connections, may contribute to ASD's underlying biology and support the concept of ASD subtypes with different neurobiological patterns.

Findings support ASD heterogeneity and suggest peripheral biomarkers may help identify ASD subtypes. However, clinical utility remains unclear. These molecules' roles in synaptic remodeling suggest potential therapeutic targets, though further validation studies are needed before clinical application.

Small sample size (44 ASD participants), cross-sectional design preventing causal inferences, single-site study limiting generalizability, and unclear clinical significance of the biomarker differences. The study also lacks longitudinal follow-up to assess biomarker stability over time.

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.