Association Between Serum Cytokine and Neuron-Specific Enolase Levels and the Core Symptoms of Autism Spectrum Disorder

Abstract Background Investigating alterations in blood cytokine and brain enzyme levels in autism spectrum disorder (ASD) is crucial for understanding its complex pathogenesis. Methods Between January 2021 and December 2024, all children diagnosed with ASD at the First Affiliated Hospital of Anhui Medical University who met the inclusion criteria were consecutively enrolled. Among them, 26 presented with typical features and 15 with atypical features. A control group of 24 age- and sex-matched healthy children was recruited from unrelated families. Serum levels of cytokines (IL-2R, IL-1β, IL-6, IL-8, IL-10, TNF-α) and neuron-specific enolase (NSE) were measured by Enzyme-Linked Immunosorbent Assay, and their associations with the core symptoms of ASD were analyzed. Results The ASD and control group showed statistically significant differences in serum IL-2R (P = 0.0097) and NSE (P < 0.0001) levels. In subgroup analyses, the typical and atypical ASD groups differed significantly in serum IL-2R levels (P = 0.0003), whereas the difference in NSE between subgroups was not significant after correction for multiple comparisons (P = 0.0437, q = 0.0874). Higher serum IL-2R levels were associated with more severe symptoms in children with ASD (CARS (P = 0.000), ABC (P = 0.000)). The correlation between TNF-α and ABC was of borderline significance (P = 0.030, q = 0.050). Higher serum NSE levels were associated with more severe symptoms (CARS (P = 0.048)). Serum NSE was a risk factor for ASD (P = 0.017). Serum NSE (P < 0.001), IL-2R (P = 0.014), and TNF-α (P < 0.001) had significant diagnostic value for ASD. The combined measurement of serum NSE + IL-2R + TNF-α (P < 0.001), NSE + IL-2R (P < 0.001), NSE + TNF-α (P < 0.001), and IL-2R + TNF-α (P < 0.001) also showed significant diagnostic value. Conclusion In this cross-sectional study, serum cytokines (IL-2R, TNF-α) and NSE were found to be associated with ASD. The combination of NSE with cytokines such as IL-2R and TNF-α may may be associated with distinct clinical features in children with ASD.