Comparative two‐dimensional polyacrylamide gel electrophoresis of the salivary proteome of children with autism spectrum disorder

Abstract

In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P-value <0.05 or a fold change of ≥3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha-amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down-regulated in ASD. Increased expression of proto-oncogene Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible protein precursor, Mucin-16, Ca binding protein migration inhibitory factor-related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

“…90 Regarding the M4 phenotype, the modulatory effect correlates strongly with the CXCL-4-mediated response that directly influences cell differentiation. 48,91,92 This was confirmed mainly by approaches investigating the development of atherosclerosis where the appearance of foamy macrophages with overexpressed genes, such as GM-CSF, CCL18, CD86, TNFSF10, ALOX5, IL1RN,and AIF1, induced production of pro-inflammatory mediators. In addition, development of the immune response in the processing and presentation of antigens by this cell triggers a regulatory phenomenon leading to overexpression of CD86, HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DQA1.…”

Depletion of stercobilin in fecal matter from a mouse model of autism spectrum disorders

“…While a GUT for ASD etiology may be unrealistic due to the heterogeneity in causation and severity, the search for potential biomarkers with a focus on metabolites has gained considerable momentum in the past decade (Adamo et al 2014; Altieri et al 2011; Dager et al 2015; Dieme et al 2015; Durieux et al 2016; Faber et al 2009; Gabriele et al 2014; Goldenthal et al 2015; Gorrindo et al 2013; Herbert et al 2006; Jyonouchi et al 2008; Masi et al 2017; Ming et al 2012; Ming et al 2005; Pastural et al 2009; Ramsey et al 2013; Rudolph et al 2013; Woods et al 2015; James et al 2004; Frye et al 2013; Ngounou Wetie et al 2015). Expanding the search to identify potential subgroups within ASD has been of interest.…”

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