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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Biomarkers 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.

Results

S100A9, 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.

Conclusions

Tears 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 material

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

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

Juvenile idiopathic arthritis.

Angelo Ravelli, Alberto Martini (2007)

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways.

0 comments Cited 419 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

Lara Aqrawi, Hilde Galtung, Beate Vestad … (2017)

Background There is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sjögren’s syndrome (pSS) patients. Incorporation of additional diagnostics involving screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients. Methods Liquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis. Results Upregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-α signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive immune response in saliva, of cellular component assembly for saliva EVs, and of metabolism and protein folding in tears in pSS patients. Conclusions LC-MS of saliva and tears from pSS patients, solely and in combination with size-exclusion chromatography allowed screening for possible novel biomarkers encompassing both salivary and lacrimal disease target organs. This approach could provide additional diagnostic accuracy in pSS, and could possibly also be applied for staging and monitoring the disease. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1228-x) contains supplementary material, which is available to authorized users.

0 comments Cited 86 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines.

A Heiligenhaus, M Niewerth, G Ganser … (2007)

To analyse the prevalence and complications of uveitis and their predictors in a large cohort of patients with juvenile idiopathic arthritis (JIA). Data of 3271 JIA patients as classified by International League of Associations for Rheumatology (ILAR) criteria included in a national database during 1 yr were analysed. Uveitis prevalence was 12% of all JIA patients. The most frequent were oligoarthritis extended (25%) and persistent (16%). JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs 7.0 yrs) or ANA-positive (86% vs 42%) than the patients without uveitis. Predictors of uveitis included age at onset (P= 0.03) and ANA-positivity (P< 0.01) besides the presence of a certain JIA subgroup (P= 0.04). Uveitis was clinically silent in 75% of the oligoarthritis but in none of the enthesitis-related arthritis patients. The median onset of uveitis was 5.5 months after arthritis manifestation. In 73%, 77% and 90%, uveitis developed within 1, 2 and 4 yrs after arthritis, respectively. Anterior uveitis was the most common anatomic type of uveitis (83%). Uveitis complications at mean follow-up of 5.6 yrs were common (56%), and predictors for complications included presence of complications at first visit (P< 0.001) and uveitis manifestation before arthritis (P= 0.001), but not ANA positivity. The JIA subgroups markedly differ with respect to the prevalence and course of associated uveitis. Ophthalmological screening should be initiated early after arthritis onset and the intervals be related to the JIA subgroup. A modification of the current screening guidelines is suggested.

0 comments Cited 82 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Sheila T. Angeles-Han: sheila.angeles-han@cchmc.org

Journal

Journal ID (nlm-ta): J Ophthalmic Inflamm Infect

Journal ID (iso-abbrev): J Ophthalmic Inflamm Infect

Title: Journal of Ophthalmic Inflammation and Infection

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Electronic): 1869-5760

Publication date (Electronic): 16 October 2018

Publication date PMC-release: 16 October 2018

Publication date Collection: 2018

Volume: 8

Electronic Location Identifier: 17

Affiliations

[1 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Division of Rheumatology, , Cincinnati Children’s Hospital Medical Center, ; 3333 Burnet Avenue, MLC 4010, Cincinnati, OH 45229 USA

[2 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Department of Pediatrics, , University of Cincinnati, ; Cincinnati, OH USA

[3 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Ophthalmology, Emory Eye Center, , Emory University School of Medicine, ; 1365 Clifton Rd B, Atlanta, GA 30322 USA

[4 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Emory Integrated Proteomics Core, , Emory University, ; 1510 Clifton Rd, Atlanta, GA 30322 USA

[5 ]GRID grid.414408.d, Childrens Healthcare of Atlanta, Emory Children’s Center, ; 2015 Uppergate Drive, Atlanta, GA 30322 USA

[6 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Pediatrics, , Emory University School of Medicine, ; Atlanta, GA USA

[7 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Human Genetics, , Emory University School of Medicine, ; Atlanta, GA USA

[8 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, , University of Cincinnati, ; 3333 Burnet Avenue, MLC 5041, Cincinnati, OH 45229 USA

[9 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, UCLA Stein Eye Institute and David Geffen School of Medicine at University of California, ; 100 Stein Plaza, Los Angeles, CA 90095-7000 USA

Article

Publisher ID: 156

DOI: 10.1186/s12348-018-0156-5

PMC ID: 6191408

PubMed ID: 30327966

SO-VID: 89c4f2e3-57c8-4f45-9fe6-0253681bd555

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.