Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

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 (CD14hi/CD16-), and non-classical monocytes (CD14low/CD16+) compared to TD children (p < 0.001). Elevated levels of classical monocytes (beta: 0.395; 95 %CI: 0.260-0.530; p < 0.001) and non-classical monocytes (beta: 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.