In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P-value <0.05 or a fold change of ≥3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha-amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down-regulated in ASD. Increased expression of proto-oncogene Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible protein precursor, Mucin-16, Ca binding protein migration inhibitory factor-related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.

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Approximately 1/68 children are believed to be affected by Autism Spectrum Disorder (ASD). A survey study suggests numbers as high as 1/50. With the increased diagnosis of ASD, treatment and understanding of the disorder is a pressing health concern. Protein biomarkers found for ASD may be used for ASD diagnosis, subtyping, monitoring, treatment, identifying therapeutic targets and may also provide clues about the causes of ASD. Here, saliva samples from 14 children with ADOS‐2 diagnosed ASD and 14 age and gender matched controls were analyzed using a combination of gel electrophoresis, in gel digestion or in solution digestion and nanoliquid chromatography‐tandem mass spectrometry (nanoLC‐MS/MS) to investigate differences between the proteomes of ASD subjects and matched controls. These results will hopefully shed light on possible causes of ASD and confirm our previous findings. In a preliminary 6 vs. 6 analysis using saliva from males, in solution digestion and analysis identified numerous proteins involved in immune responses to be dysregulated. Two of these proteins were lactotransferrin, involved in gastrointestinal antimicrobial activity, and prolactin inducible protein, involved in immune responses, which were upregulated in ASD compared to controls. Additional dysregulated proteins were also detected in blood serum, suggesting an enhanced response to environmental toxic factors. This investigation is ongoing.Support or Funding InformationASPIRE Fellowship, Shire, T. Urling and Mabel Walker Research Fellowship Program, SUNY Plattsburgh Presidential Research Award