Discovery of tear biomarkers in children with chronic non-infectious anterior uveitis: a pilot study

Sheila T Angeles-Han,Gary N Holland,Sampath Prahalad,Mekibib Altaye,Sherry Thornton,Ndate Fall,Kelly A Rouster-Stevens,Kirsten Jenkins,Steven Yeh,Purnima Patel,Duc Duong

doi:10.1186/s12348-018-0156-5

Abstract

BackgroundBiomarkers in easily obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. Aqueous humor has been studied for biomarkers, but is not routinely available. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor.In this pilot study, we used Schirmer strips to collect tears from seven children (nine eyes); three children had JIA- associated uveitis (JIA-U) and four had idiopathic disease (I-CAU). Liquid chromatography-tandem mass spectrometry was used to identify and quantify tear proteins. The Mann-Whitney U test identified differential tear protein expression between children with JIA-U and those with I-CAU.ResultsS100A9, LAP3, TTR, MIF, sCD14, S100A8, and SAA1 were detected in tears of all children; the same cytokines have been reported in aqueous humor of children with JIA-U. Tears from children with JIA-U had higher expression of proteins associated with inflammatory arthritis (SEMA3G, TIMP1, HEXB, ERN1, and SAA1) than tears from those with I-CAU. In addition, we found higher expression of sCD14, S100A8, and SAA1, but lower expression of S100A9, LAP3, TTR, and MIF, in tears from children with JIA-U compared to tears from those with I-CAU.ConclusionsTears contain similar cytokine profiles to aqueous humor in children with CAU and may be a clinically useful source of disease biomarkers. Tears from children with JIA-U also contain cytokines associated with inflammatory arthritis; furthermore, differential expression of other tear proteins as well may provide clues to intrinsic differences between JIA-U and I-CAU, despite their similar clinical phenotypes.

Highlights

Biomarkers in obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed
Analysis of tears may be a non-invasive approach to assess biomarkers of uveitis, in order to identify children with JIA who are most susceptible to uveitis, and it may be reflective of intraocular pathology
Our objectives were to use tears to (1) determine if cytokines and chemokines reported to be present in aqueous humor (AqH) of children with uveitis are observed in tears and (2) assess the comparative tear proteomic milieu in children with JIAassociated uveitis (JIA-U) and I-chronic anterior uveitis (CAU)

Summary

Introduction

Biomarkers in obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor. In this pilot study, we used Schirmer strips to collect tears from seven children (nine eyes); three children had JIAassociated uveitis (JIA-U) and four had idiopathic disease (I-CAU). Idiopathic chronic anterior uveitis (I-CAU) and JIA-associated uveitis (JIA-U) have similar clinical phenotypes, inflammatory arthritis is not present in children with I-CAU. Children at highest risk for uveitis are those with oligoarticular and polyarticular rheumatoid factor (RF)-negative JIA, who are < 7 years old at JIA onset, with < 4 years duration of JIA, and who are antinuclear antibody (ANA)-positive These factors are not, adequate to stratify risk accurately [6, 7]. Differences in the levels of cytokines and chemokines have been reported in the tears of adults with uveitis compared to healthy subjects [16]

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