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.
Highlights
The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years
Multiplex immunoassay Multiplex immunoassay profiling of serum samples resulted in identification of 16 analytes that were present at significantly different levels between drug-free individuals with AS (n = 30) and controls (n = 29) after adjustment for age, Body mass index (BMI), and exercise (Table 2)
The analytes showing the largest ratiometric differences included neuronal cell adhesion molecule that was increased with a ratio of 1.4 in AS compared to controls, and fatty acid binding protein and growth hormone that were decreased with ratios less than 0.5
Summary
The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. Previous multiplex immunoassay profiling studies targeting specific classes of proteins have identified diagnosis-sex interactions in serum molecules such as cytokines, steroid and metabolic hormones, growth factors and lipid transport in adults with AS [6,7]. In these studies, females with AS had a higher number of changes in the levels of lipid and hormone-related molecules, and males with AS showed more changes in molecules related to dysfunction of immune or inflammatory pathways. This can make interpretation of the results of proteomic analyses difficult as the findings may be affected by drug- and lifestyle-related confounding factors
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