Circulating Soluble Urokinase Plasminogen Activator Receptor and C-Reactive Protein Concentrations in Adults with High-Functioning Autism

Abstract

Background: Immune dysregulation has been implicated in the pathophysiology of autism spectrum disorder (ASD). Soluble urokinase plasminogen activator receptor (suPAR) is a stable biomarker of chronic immune activation that has not previously been investigated in ASD. We compared circulating suPAR and C-reactive protein (CRP) concentrations in adults with high-functioning ASD and healthy controls. Methods: In this cross-sectional case–control study, 38 adults with high-functioning ASD and 37 healthy controls were included. Plasma suPAR and CRP concentrations were measured using enzyme-linked immunosorbent assays. Group differences were examined using hierarchical multiple linear regression analyses adjusting for age, sex, body mass index (BMI), and current smoking status. The Autism Spectrum Quotient (AQ) was administered to all participants, and associations between inflammatory biomarkers and autistic traits were assessed using Spearman’s rank correlation analyses. Sensitivity analyses were performed after excluding participants with CRP concentrations > 10 mg/L to minimise the potential influence of acute inflammatory conditions. Results: In unadjusted analyses, CRP concentrations were significantly higher in the ASD group (p = 0.006), whereas suPAR concentrations did not differ (p = 0.163). After adjustment for age, sex, BMI, and smoking status, the association between ASD and CRP was no longer significant (p = 0.181), with BMI emerging as the strongest independent predictor of CRP (p < 0.001). No association was observed between ASD and circulating suPAR concentrations in either unadjusted or adjusted analyses (p = 0.612). CRP, but not suPAR, was positively correlated with AQ total scores (p = 0.026). Sensitivity analyses excluding participants with high CRP concentrations yielded findings consistent with the primary analyses. Conclusions: Adults with high-functioning ASD showed no evidence of elevated circulating suPAR concentrations. The attenuation of CRP group differences after adjustment for BMI and smoking status highlights the importance of accounting for metabolic factors when interpreting peripheral inflammatory biomarkers in ASD. These findings do not support elevated suPAR levels in adults with high-functioning ASD.