Proteomics Study of Peripheral Blood Mononuclear Cells (PBMCs) in Autistic Children

Abstract

Autism is one of the most common neurological developmental disorder associated with social isolation and restricted interests in children. The etiology of this disorder is still unknown. There is neither any confirmed laboratory test nor any effective therapeutic strategy to diagnose or cure it. To search for biomarkers for early detection and exploration of the disease mechanisms, here, we investigated the protein expression signatures of peripheral blood mononuclear cells (PBMCs) in autistic children compared with healthy controls by using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach. The results showed a total of 41 proteins as differentially expressed in autistic group as compared to control. These proteins are found associated with metabolic pathways, endoplasmic reticulum (ER) stress and protein folding, endocytosis, immune and inflammatory response, plasma lipoprotein particle organization, and cell adhesion. Among these, 17 proteins (13 up-regulated and four down-regulated) are found to be linked with mitochondria. Eight proteins including three already reported proteins in our previous studies were selected to be verified. Five already reported autism associated pro-inflammatory cytokines [interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α)] were detected in plasma by enzyme-linked immunosorbent assay (ELISA) analysis. The results were consistent with proteomic results and reports from previous literature. These results proposed that PBMCs from autistic children might be activated, and ER stress, unfolded protein response (UPR), acute-phase response (APR), inflammatory response, and endocytosis may be involved in autism occurrence. These reported proteins may serve as potential biomarkers for early diagnosis of autism. More specifically, simultaneous detection of three proteins [complement C3 (C3), calreticulin (CALR), and SERPINA1] in the plasma and PBMCs could increase the authenticity of detection.

A Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project

“…There has been intense interest in discovering easily implementable biomarkers that support screening, diagnosis, and targeted intervention of ASD [McPartland, 2017;Riedl, Gieger, Hauner, Daniel, & Linseisen, 2017]. Diverse modalities of biomarkers have been investigated including neuroimaging, EEG, eye tracking, pupillary reflex, and transcriptomic, proteomic, and metabolomics markers [Bridgemohan et al, 2019;Broek et al, 2014;Ruggeri, Sarkans, Schumann, & Persico, 2014;Shen et al, 2019]. Potential metabolic biomarkers of ASD have been identified, mainly in blood or urine, using a variety of analytical approaches that have suggested that a range of metabolic processes are altered in ASD [De Angelis et al, 2013;Glinton & Elsea, 2019;Lanz et al, 2013;Ming, Stein, Barnes, Rhodes, & Guo, 2012;Ming et al, 2005;Orozco, Hertz-Picciotto, Abbeduto, & Slupsky, 2019;Yap et al, 2010].…”

Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

“…More specifically, differences in protein signature between subgroups of Rett syndrome have been identified [107]. Bottom-up proteomics have revealed consistent changes in proteins involved in mitochondrial function, ER stress and protein folding, endocytosis and immune response, and metabolites, including in children with mental regression [108,109]. Wei et al identified reduced levels of the STOP/MAP6 protein in the blood plasma of autistic children [110].…”

Inflammation (IL-1β) Modifies the Effect of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids on Core Symptoms of Autism Spectrum Disorder—An Exploratory Pilot Study

“…Furthermore, growing evidence suggest an ongoing immune dysfunction in the brain and the peripheral immune system of a subset of individuals with ASD [5,6]. Several peripheral markers of inflammation (interleukin-1 beta (IL-1β), IL-6 and tumour necrosis factor-alpha (TNF-α)) have been found to be elevated in children with ASD [7][8][9][10][11].…”

“…Several reports from human studies also suggest that gestational vitamin D and/or omega-3 LCPUFA deficiency is associated with the development of ASD [38][39][40][41] and other psychological and neurodevelopmental disorders [42]. Furthermore, children with ASD have been shown to have inadequate intakes of vitamin D and omega-3 LCPUFA [11][12][13][14][15], as is reflected in significantly lower vitamin D and/or omega-3 LCPUFA status than their healthy counterparts [5,16].…”