Elevated serum levels of macrophage-derived chemokine and thymus and activation-regulated chemokine in autistic children

Laila Yousef Al-Ayadhi,Gehan Ahmed Mostafa

doi:10.1186/1742-2094-10-72

Abstract

BackgroundIn some autistic children, there is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children. Th2 lymphocytes express CCR4 receptors. CCR4 ligands include macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). They direct trafficking and recruitment of Th2 cells. We are the first to measure serum levels of CCR4 ligands in relation to the degree of the severity of autism.MethodsSerum concentrations of MDC and TARC were measured, by quantitative sandwich enzyme immunoassay technique, in 56 autistic children and 32 healthy matched children.ResultsAutistic children had significantly higher serum levels of MDC and TARC than healthy controls (P <0.001 and P <0.001, respectively). Children with severe autism had significantly higher serum levels of MDC and TARC than patients with mild to moderate autism (P <0.001 and P = 0.01, respectively). In addition, there were significant positive correlations between CARS and serum levels of both MDC (P <0.001) and TARC (P <0.001) in children with autism. There were significant positive correlations between serum levels of MDC and TARC in autistic children (P <0.001).ConclusionsSerum levels of CCR4 ligands were elevated in autistic children and they were significantly correlated to the degree of the severity of autism. However, further research is warranted to determine the pathogenic role of CCR4 ligands in autism and to shed light on the therapeutic role of CCR4-ligand antagonism in autistic children.

Highlights

In some autistic children, there is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children
Children with severe autism had significantly higher serum levels of macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) than patients with mild. Serum levels of both MDC and TARC had no significant correlations with the age of the children with autism (P = 0.87 and P = 0.47), respectively
There were no significant correlations between the Body mass index (BMI) and serum levels of both MDC (P >0.05) and TARC (P >0.05) in children with autism

Summary

Introduction

There is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children. CCR4 ligands include macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). They direct trafficking and recruitment of Th2 cells. Inflammation is characterized by the local tissue expression of chemokines, a large group of chemotactic cytokines, which play an important pathogenic role in inflammatory diseases by enhancement of leukocyte recruitment and activation at inflammatory sites [1,2,3,4]. CCR4 ligands, MDC and TARC, act on their CCR4 receptors to enhance the recruitment and activation of T helper (Th) 2 cells with a subsequent production of type 2 cytokines that include interleukin-4 (IL-4), IL-5, IL-9 and IL-13 [9,10]. Chemokines and their receptors have been implicated as functional mediators of immunopathology of autoimmune neuroinflammatory diseases [19,20]

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