Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

Abstract

BackgroundThe higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum.MethodsHere, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS.ResultsMultiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.ConclusionTaken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.

iTRAQ‐Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism

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A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder

“…There is however, evidence for different protein blood biomarkers in males and females with ASD, specifically Asperger's syndrome. A recent MS study reported that females had differences in proteins related to lipid transport/metabolism versus controls, whiles males with Asperger's syndrome primarily had differences in inflammatory proteins [Steeb et al, ], confirming a prior study showing similar differences in adult males and females with Asperger's syndrome [Schwarz et al, ]. Our current results support that inflammatory biomarkers are present in males with ASD in the salivary proteome, but we do not yet know if the current protein signature generalizes to females.…”

Sex Differences in Autism Spectrum Disorder: a Review

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