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Sheila T Angeles-Han, Steven Yeh, Purnima Patel, Duc Duong, Kirsten Jenkins, Sampath Prahalad, Gary N Holland; Tear Proteomics in Pediatric Chronic Non-infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2155.
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© ARVO (1962-2015); The Authors (2016-present)
Children with juvenile idiopathic arthritis (JIA) have increased uveitis risk. ANA guides the uveitis screening schedule, but there are no definitive predictors. Potential biomarkers were found in serum and aqueous humor. Tear proteomics may better identify JIA children at greatest risk for uveitis. Collection is less invasive, easily accessible and better tolerated. We examined the tear profile of JIA-associated uveitis (JIAU), idiopathic chronic anterior uveitis (CAU) and other forms of idiopathic uveitis (other U) to identify potential biomarkers.
We collected tear samples from JIAU, CAU and other U children who were >10 years old (Table 1). We placed a Schirmer strip 6mm from the lateral canthus of the anesthesized eye for 2-5 minutes. Then, 50 ug of proteins were extracted for TMT labeling. TMT pool was loaded onto an offline electrostatic repulsion interaction chromatography (ERLIC) fractionation HPLC system and 20 fractions were collected. LC-MS/MS analysis was done on all 20 fractions. Proteome Discoverer 2.1 (ThermoFisher Scientific, San Jose, CA) was used to search all the MS/MS spectra against a Uniprot human reference protein database (retrieved April 20, 2015; 90,411 target sequences) and TMT reporter quantitation was done.We compared 1) JIAU to CAU and other U; 2) JIAU to CAU using ANOVA.
We quantified 1483 unique protein groups and 120 proteins had statistically significant differences in expression. Of those proteins, 12 were significant across JIAU vs. CAU and other U. Most significant were PTK7 (p=0.004), GART (p=0.008), IGFBP6 (p=0.011), TM9SF1 (p=0.014), FTH1 (p=0.024), PSMB6 (p=0.034), and CDKN2C (p=0.04). Gene ontology showed pathways related to amylase activity, growth regulation and response to stimulus.When we restricted analysis to JIAU vs. CAU, SAA1 (p=0.002), DPP3 (p=0.022), ALDH9A1 (p=0.035), and CDKN2C (p=0.043) were significant. Gene ontology showed pathways related to amylase activity, proteolysis and peptidase activity.CDKN2 was increased in CAU and other U compared to JIAU. SAA1 was increased in JIAU compared to CAU, but not other U. SAA1 gene polymorphisms are reported in rheumatoid arthritis.
We identified potential biomarkers for JIAU using tear proteomics. Tear collection is a non-invasive, easily accessible and well-tolerated method which allows study in JIA alone. Biomarker discovery in JIAU will aid early detection of uveitis in JIA children at highest risk.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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