Novel Inflammatory Biomarkers for Autism Spectrum Disorder Detected by Plasma Olink Proteomics

Background: Research evidence has recently shown an association between autism spectrum disorder (ASD) and inflammation. For example, the expression of inflammatory cytokines is abnormal in children with ASD, and maternal inflammation can lead to ASD-like behavior in offspring. These studies suggest that inflammation plays an important role in the occurrence and development of ASD. Inflammatory cytokines may, therefore, be potential biomarkers for ASD. In the present study, we sought to systematically identify inflammatory biomarkers of children with ASD. Methods: We used Olink proteomics to comprehensively examine differentially expressed inflammation-related proteins in 60 children with ASD and 28 children with typical development (TD). We validated our findings using published data. Results: A total of 18 inflammation-related proteins were differentially expressed between the ASD and TD groups. Compared with the TD group, the expression of all differentially expressed proteins was up-regulated in the ASD group. Furthermore, eight differentially expressed proteins showed good diagnostic efficacy, as delineated by area under the curve (AUC) values of > 0.7. To our knowledge, this is the first time that up-regulated interleukin-17C (IL-17C), chemokine ligand (CCL)-19, and CCL20 have been detected in the plasma of children with ASD (with AUC of 0.839, 0.763, and 0.756, respectively). We also found that there was a negative correlation between inflammatory cytokines and SRS scores. Conclusions: Multiple inflammatory markers were increased in children with ASD. IL-17C, CCL19, and CCL20 exhibit potential as biomarker candidates for ASD. Elevated expression levels of cytokines may enhance social ability in ASD.