Distinct Cytokine and Chemokine Profiles in Autism Spectrum Disorders.

Yvonne M Y Han,Timmy W S Cheng,Agnes S Chan,Winnie K Y Cheung,Sophia L Sze,Michael K Yeung,Chun Kwok Wong

doi:10.3389/fimmu.2017.00011

Abstract

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). However, this research has been conducted almost exclusively in Western contexts, and only a handful of studies on immune measures have been conducted in Asian populations, such as Chinese populations. The present study examined whether immunological abnormalities are associated with cognitive deficits and problem behaviors in Chinese children with ASD and whether these children show different immunological profiles. Thirteen typically developing (TD) children and 22 children with ASD, aged 6–17 years, participated voluntarily in the study. Executive functions and short-term memory were measured using neuropsychological tests, and behavioral measures were assessed using parent ratings. The children were also assessed on immunological measures, specifically, the levels of cytokines and chemokines in the blood serum. Children with ASD showed greater deficits in cognitive functions, as well as altered levels of immunological measures, including CCL2, CCL5, and CXCL9 levels, compared to TD children, and the cognitive functions and associated behavioral deficits of children with ASD were significantly associated with different immunological measures. The children were further sub-classified into ASD with only autistic features (ASD-only) or ASD comorbid with attention deficit hyperactivity disorder (ASD + ADHD). The comorbidity results showed that there were no differences between the two groups of ASD children in any of the cognitive or behavioral measures. However, the results pertaining to immunological measures showed that the children with ASD-only and ASD + ADHD exhibited distinct cytokine and chemokine profiles and that abnormal immunologic function was associated with cognitive functions and inattention/hyperactivity symptoms. These results support the notion that altered immune functions may play a role in the selective cognitive and behavioral symptoms of ASD.

Highlights

One essential finding in autism spectrum disorder (ASD) research has been the consistent immunological abnormality detected among autistic individuals
The findings of the present study showed deviated concentrations of serum cytokines and chemokines, with elevated macrophage/ monocytes CCL2 and levels of the Th2-related chemokine CCL5 and reduced levels of the T helper type 1 (Th1)-related chemokine CXCL9 in children with ASD compared to typically developing (TD) controls
The deviations in CCL5 and CXCL9 were linked to impairments in the behavioral domains, with associations observed between more behavioral problems measured in the three behavioral domains, including social communication/interaction, repetitive/restricted behavior, and inattention/hyperactivity, and increased levels of CCL5 and decreased CXCL9, such that impairments in the behavioral domains were more pronounced in individuals with deviations in the concentrations of these two chemokines

Summary

Introduction

One essential finding in autism spectrum disorder (ASD) research has been the consistent immunological abnormality detected among autistic individuals. Altered levels of TGFβ1 have been found in plasma and serum specimens of ASD compared with TD controls [8,9,10] These findings suggest that the increased inflammatory chemokine and cytokine production detected in the brain and peripheral blood of autistic individuals may produce a profoundly negative effect on proper neuronal development, migration, differentiation, and synapse formation and subsequently affect the behavior of individuals with ASD [1, 11, 12]. Consistent with these findings, cytokine and chemokine levels have been shown to correlate with the severity of behavioral abnormalities in individuals with ASD. Significant associations between increased plasma levels of CCL5 and CXCL8 and more frequent aberrant behaviors and fewer adaptive behaviors have been found [3, 6]

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Conclusion