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Urine Protein Biomarker Candidates for Autism

Libang Yang, Kyle Rudser, Allison Golnik, Andrew Wey, Lee Ann Higgins and Glenn R Gourley

Autism Spectrum Disorder (ASD) is increasingly common and treatment is most successful if instituted early in life. Urine biomarkers of autism could hasten diagnosis as urine is easy to obtain non-invasively. The purpose of this research was to compare urine samples from 8 ASD subjects and 8 age- and gender-matched controls. Samples were analyzed with isobaric Tags with Relative and Absolute Quantitation (iTRAQ™), a mass spectrometry method which enables identification and relative quantification of many proteins. We identified 231 proteins present in at least two control and two Autism subjects for statistical analysis. We ranked the proteins according to the P-values between Autism and control groups. The top five proteins were increased in ASD subjects compared to controls and included alpha 1-acid glycoprotein, prostaglandin-H2 D-isomerase, kininogen-1 isoform 2, leucine-rich alpha-2- glycoprotein 1 and immunoglobulin fragment Fab New lambda light chain. Two of the top 10 proteins have previously been related to autism, while six have previously been related to inflammation. We analyzed the 231 proteins with Ingenuity Pathway Analysis (IPA) to assess pathways involved and potential biomarkers. 104 of the 231 proteins were suggested by IPA as possible biomarkers in urine. The remaining 127 urinary proteins we identified are novel as they are not included as IPA urinary proteins. These research data fit with some current hypotheses regarding autism and suggest a relationship between ASD, inflammation and gastrointestinal disease. Specific urinary proteins are identified which could potentially serve as biomarkers for ASD.