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

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.Electronic supplementary materialThe online version of this article (10.1186/s12348-018-0156-5) contains supplementary material, which is available to authorized users.

Juvenile Idiopathic Arthritis Associated Uveitis

“…Because of the relative difficulty and invasiveness of sampling AqH, tear collection has been suggested for protein analysis in the context of uveitis. In a pilot study on three children with JIA-uveitis, elevated levels of proteins associated with inflammatory arthritis (SEMA3G, TIMP1, HEXB, ERN1, and SAA1) was found, in addition to elevated levels of sCD14, S100A8, and SAA1, but reduced levels of S100A9, LAP3, TTR, and MIF [87]. Previously, tear levels of IL-1RA, IL-8, fractalkine, IP-10, VEGF, and TGF-β2 had been shown to be elevated in uveitis [100], although this study encompassed multiple diverse forms of uveitis and not specifically JIA-associated uveitis.…”

Interleukins and cytokine biomarkers in uveitis

“…Recent advances in molecular diagnostic and personalized proteomics analysis of ocular samples were able to identify different biomarkers in various ocular inflammation [ Table 12 ]. [ 116 117 118 119 120 121 ] Identification of these biomarkers has opened new gates for additional accuracy of diagnosis, targeted treatment, and avoiding unnecessary drugs, thereby reducing the systemic side effects and improving the quality of life. [ 116 117 ] Future trends of treatment include IL-6, IL-23, and mTOR inhibitor and complement directed therapies (clinicaltrials.gov NCT01526889).…”

Protein Biomarkers in Uveitis

“…This was followed by a pilot study of tears to evaluate for biomarkers in children with chronic non-infectious AU, using LC-MS/MS ( 69 ). Tears were collected from seven patients using Schirmer strips: three with JIA-associated uveitis (JIA-U), and four with idiopathic chronic anterior uveitis (I-CAU).…”