Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. Methods The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. Results After controlling for the levels of parental cytokines, we identified that interferon-alpha (IFN-alpha), interleukin-7 (IL-7), IL-8, IFN-gamma-inducible protein-10, and macrophage inflammatory protein-1 beta were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939). Conclusions Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

Automated summary

This study discovered that interferon-alpha (IFN-alpha), interleukin-7 (IL-7), IL-8, IFN-gamma-inducible protein-10, and macrophage inflammatory protein-1 beta are associated with ASD, with IL-8 being the only cytokine related to parental cytokine levels and social impairment in children with ASD. The log-transformed IL-8 level showed good discrimination between children with autism and controls, indicating its potential as a biomarker for ASD and involvement in its pathogenesis.