22505
Identification of Serum Protein Biomarkers for Autism Spectrum Disorder
Objectives: The aim of this study was to compare the levels of proteins in serum samples from 2-8 year old boys with and without ASD in order to identify possible early biological markers for ASD.
Methods: Subjects included 30 boys with ASD (mean age 5.47, SD 1.73 years) and 30 age-matched, typically developing (TD) controls (mean age 5.37, SD 1.75 years). ASD subjects underwent a diagnostic assessment using the ADOS and ADI-R. Clinical diagnosis was made based on these assessments and overall clinical impression using DSM-IV criteria. Only subjects with a diagnosis of Autistic Disorder were included. Controls were screened with the ABAS-II. To identify blood biomarkers of ASD we used the Myriad Rules Based Medicine (RBM) DiscoveryMAP to simultaneously measure a large number of proteins by multi-analyte profiling. Validation of two proteins identified from the Myriad RBM platform were subsequently performed on the MesoScales Discovery platform. Protein levels were subsequently regressed on each of the ADOS subdomain scores to determine whether they were related to a clinical measure of ASD.
Results: There were 11 proteins, 7 of which were significantly different between the two groups (p<0.05), which collectively predicted ASD vs. TD samples. Cross-validation of two proteins, thyroid stimulating hormone (TSH) and interleukin-8 (IL-8), was performed on 43 ASD boys (mean age 5.08, SD 1.77 years) and 37 TD boys (mean age 5.09, SD 1.86 years) for TSH, and 36 ASD boys (mean age 5.46, SD 1.61 years) and 35 TD boys (mean age 5.69, SD 1.94 years) for IL-8. TSH levels were 30% lower in ASD boys whereas IL-8 levels were 16% higher in ASD boys. When combining the levels of TSH and IL-8 to predict ASD, the predictive accuracy was 82%. Three ADOS subdomains exhibited a significant negative effect whereby higher scores in the subdomains (i.e. more ASD symptoms) were associated with lower levels of TSH: social interaction (z=-2.61, p=0.009), communication + social interaction (z =-2.12, p=0.034), and stereotyped behavior and restrictive interests (SBRI) (z=-2.28, p= 0.023). There was not a significant relationship between TSH and the ADOS communication subdomain, or IL-8 and any of the ADOS subdomain scores.
Conclusions: These data suggest that a panel of serum proteins can be useful as a blood biomarker for ASD in boys.