Abstract

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder whose etiology is poorly understood. Recent studies have shown that autistic children may be experiencing increased inflammation and oxidative stress. Altered immune regulation may be one contributing factor to inflammation and oxidative stress in autistic children. Sulfur amino acid (SAA) metabolism plays a critical role in regulating blood leukocyte functions and oxidative stress. However, it is not known whether autism impacts SAA metabolism in peripheral immune cells. To address this question, a novel liquid chromatography linked tandem mass spectrometric (LC/MS/MS) method was used to determine the levels of SAA metabolites in peripheral blood mononuclear cells obtained from 11 healthy controls and 31 autistic children. Improved detection sensitivity and selectivity of the LC/MS/MS method allowed accurate quantification using small samples. Results show that leukocytes from autistic children contained significantly lower concentrations of S-adenosylmethionine (-35%; p = 0.01), and elevated levels of intracellular homocysteine content (+80%; p=0.003). Additionally, the levels of intracellular total cysteine and glutathione (GSH) were reduced by 39% (p=0.004) and 25% (p=0.01), respectively. These autism-associated changes were leukocyte specific in that no significant alterations in SAA metabolite concentrations were detected in the plasma samples. Our results provide novel evidence for altered metabolism in immune cells; furthermore, this data suggest the involvement of inflammation in autism. Dietary differences between controls and patients, however, remain a potential confounder.

Highlights

  • Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no established genetic or biochemical biomarkers

  • A recent Center for Disease Control (CDC) report estimates that 1 in 150 children are afflicted by this disorder, making autism one of the most prevalent childhood neurodevelopmental disorders [2]

  • A more collection from 11 healthy controls and 31 children comprehensive analysis of Sulfur amino acid (SAA) metabolism was diagnosed with ASD were performed at the Pfeiffer performed in studies published by James et al [16,17]

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Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no established genetic or biochemical biomarkers. It has been the control and ASD children were supplemented with shown that autism may be associated with a decline in any nutritional supplements or prescription medications cell-mediated adaptive immunity, as indicated by for at least six months prior to the collection of the reports of decreases in Th1-related cytokines such as sample data. Studies have found that urinary and whether SAA metabolism in the leukocytes was plasma levels of lipid oxidation markers in autistic affected in autistic children.

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