Altered monocyte subpopulations and their association with autism spectrum disorder risk in children

Abstract

Objective

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Emerging evidence suggests a link between immune dysregulation and ASD. This study investigates alterations in monocyte subpopulations and cytokine production in children with ASD and their potential associations with ASD risk and severity.

Methods

Initially, the immune status of peripheral blood mononuclear cells was assessed in cohort-I of 96 typically developing (TD) children and 92 children diagnosed with ASD using flow cytometry. Subsequently, the secretion of cytokines IL-6 and IL-10 by monocytes was evaluated following stimulation with a leukocyte activation mixture and intracellular protein staining technique in cohort-II.

Results

Children with ASD exhibited significantly higher levels of total monocytes, classical monocytes (CD14^hi/CD16^–), and non-classical monocytes (CD14^low/CD16⁺) compared to TD children (p < 0.001). Elevated levels of classical monocytes (β: 0.395; 95 %CI: 0.260–0.530; p < 0.001) and non-classical monocytes (β: 0.629; 95 %CI: 0.516–0.742; p < 0.001) were significantly associated with ASD after adjusting for age, sex and body mass index. Furthermore, increased production of IL-6 by monocytes was observed in children with ASD (p = 0.001). Logistic regression analysis revealed that classical monocytes (OR: 1.104; 95 %CI: 1.062–1.147; p < 0.001), non-classical monocytes (OR: 2.913; 95 %CI: 2.130–3.986; p < 0.001) and IL-6 production by monocytes (OR: 1.306; 95 %CI: 1.096–1.557; p = 0.003) are risk factors for ASD. Spearman correlation analysis revealed a negative correlation between classical monocyte levels and adaptive behavior developmental quotient (DQ) (r = − 0.377; p = 0.001), fine motor DQ (r = − 0.329; p = 0.003) and personal-social DQ (r = − 0.247; p = 0.029) in children with ASD.

Conclusion

Elevated classical and non-classical monocytes are potential risk factors for ASD and may influence neurodevelopmental outcomes. Further research is needed to elucidate the precise mechanisms and therapeutic implications.