Abstract
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.
Highlights
It is estimated that 1 in 88 children in the USA have autism spectrum disorder (ASD) with a worldwide average prevalence of about 1% [1].Diagnosis of ASD is based on DSM behavioral criteria and best addressed by a multi-disciplinary team, utilizing standardized tools and laboratory evaluation for co-existing conditions
Urine biomarkers of autism would be very useful as urine is easy to obtain non-invasively and diagnosis could be hastened
We present data regarding potential urine biomarkers discovered with the use of isobaric Tags for Relative and Absolute Quantitation, a proteomic method not previously used for ASD biomarker discovery
Summary
It is estimated that 1 in 88 children in the USA have autism spectrum disorder (ASD) with a worldwide average prevalence of about 1% [1].Diagnosis of ASD is based on DSM behavioral criteria and best addressed by a multi-disciplinary team, utilizing standardized tools and laboratory evaluation for co-existing conditions. Despite the fact that symptoms are often present before age 2 [2,3], the average age of diagnosis was 3.1 years for children with autistic disorder, 3.9 years for pervasive developmental disorder not otherwise specified, and 7.2 years for Asperger’s disorder [4]. Surveyed parents of children with autism waited almost three years to receive a diagnosis following their first visit to a professional regarding their child’s development [6]. Urine biomarkers of autism would be very useful as urine is easy to obtain non-invasively and diagnosis could be hastened. Proteomic methods have been advocated for discovery of autism biomarkers [8]. We present data regarding potential urine biomarkers discovered with the use of isobaric Tags for Relative and Absolute Quantitation (iTRAQ), a proteomic method not previously used for ASD biomarker discovery
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