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Altered monocyte subpopulations and their association with autism spectrum disorder risk in children
Wenhua Li1, Lingling Zhang2, Yiran Xu2
1Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg 40530, Sweden.
Insights
Elevated levels of classical and non-classical monocytes, along with increased IL-6 production, are identified as potential risk factors for autism spectrum disorder (ASD) in children. These immune alterations may also impact neurodevelopmental outcomes.
Area of Science:
- Immunology
- Neurodevelopmental Disorders
- Pediatrics
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with increasing evidence linking immune system dysregulation to its pathophysiology.
- Understanding the role of immune cells, such as monocytes, and their cytokine production in ASD is crucial for identifying potential biomarkers and therapeutic targets.
Purpose of the Study:
- To investigate alterations in monocyte subpopulations and their cytokine production (IL-6, IL-10) in children with ASD.
- To determine the association of these immune changes with ASD risk and neurodevelopmental outcomes.
Main Methods:
- Peripheral blood mononuclear cells from children with ASD and typically developing (TD) controls were analyzed using flow cytometry to assess monocyte subpopulations.
- Cytokine secretion (IL-6, IL-10) by monocytes was measured after in vitro stimulation.
Main Results:
- Children with ASD showed significantly higher levels of total, classical, and non-classical monocytes compared to TD children.
- Elevated classical and non-classical monocyte levels, along with increased IL-6 production by monocytes, were significantly associated with ASD risk.
- Higher levels of classical monocytes correlated negatively with adaptive behavior, fine motor, and personal-social developmental quotients in children with ASD.
Conclusions:
- Increased classical and non-classical monocyte populations represent potential risk factors for ASD.
- These immune alterations may play a role in influencing neurodevelopmental outcomes in children with ASD.
- Further research is warranted to explore the underlying mechanisms and potential therapeutic strategies targeting immune dysregulation in ASD.
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 (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.
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