TY - JOUR
T1 - Potential Biomarkers for Noninfectious Scleritis Identified by Serum and Tear Fluid Proteomics
AU - Vergouwen, Daphne P. C.
AU - Kolijn, P. Martijn
AU - de Hoog, Joeri
AU - de Boer, Joke H.
AU - Los, Leonoor I.
AU - Gijs, Marlies
AU - Erckens, Roel J.
AU - de Jong, Pascal H. P.
AU - Rothova, Aniki
AU - ten Berge, Josianne C.
AU - Schreurs, Marco W. J.
N1 - Funding Information: The authors thank Ina Hidding-Bruintjes, Angelique van Veen, Sanela Kuc, and all other staff from the Erasmus Medical Center, Amsterdam University Medical Center, Utrecht University Medical Center, University Medical Center Groningen, and Maastricht University Medical Center who have contributed to patient inclusion and sample collection. The authors also thank Amber Schotting for contributing to the elution procedure of the tear fluid Schirmer strips and the MMP analysis. Further, special thanks to Nicole Nachtzaam for performing the addressable laser bead immunoassay analysis, and Sanae Boukhrissi for performing the ELISA analysis. Publisher Copyright: © 2023 American Academy of Ophthalmology
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Purpose: Scleritis is an extremely painful and potentially blinding inflammation of the sclera with unknown pathogenesis and unpredictable course. To gain insight in its disease process and identify biomarker candidates, we performed extensive proteomics in serum and tear fluid. Design: Prospective multicenter cohort study. Participants: A total of 121 patients with noninfectious scleritis (of which 39 active cases), 30 healthy controls, and 23 disease controls (uveitis and rheumatoid arthritis) were enrolled in the Netherlands from 2020 to 2022. Methods: Serum, tear fluid of both eyes, and clinical data were gathered. The level of 368 inflammatory proteins was measured using proximity extension assays. Results were validated in an independent cohort of 15 patients with scleritis, and using addressable laser bead immunoassay, or enzyme-linked immunoassays. In addition, we studied an extended panel of matrix metalloproteinases in tear fluid of necrotizing scleritis with addressable laser bead immunoassay. Main Outcome Measures: Statistically significant differences in the level of inflammatory proteins between patients with scleritis and control groups. Results: Proteomics revealed 18 significantly upregulated or downregulated serum proteins in active scleritis cases compared with all control groups in both the discovery cohort and the validation cohort. The most upregulated protein was nuclear migration protein nudC (NudC; P = 0.0032), a protein involved in neurogenesis. The other significant hits included proteins involved in T-cell activation, apoptosis, epithelial barrier maintenance, and angiogenesis. Our tear fluid analysis showed matrix metalloproteinase 9 (MMP9) to be upregulated in the tear fluid of patients with scleral necrosis. Conclusions: The results of our proteomics analysis suggest a role for neurogenesis, T-cell activation, disruption of epithelial barrier, and angiogenesis in the pathogenesis of scleritis, and highlight MMP9 and NudC as biomarkers with potential clinical relevance. Funding Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.
AB - Purpose: Scleritis is an extremely painful and potentially blinding inflammation of the sclera with unknown pathogenesis and unpredictable course. To gain insight in its disease process and identify biomarker candidates, we performed extensive proteomics in serum and tear fluid. Design: Prospective multicenter cohort study. Participants: A total of 121 patients with noninfectious scleritis (of which 39 active cases), 30 healthy controls, and 23 disease controls (uveitis and rheumatoid arthritis) were enrolled in the Netherlands from 2020 to 2022. Methods: Serum, tear fluid of both eyes, and clinical data were gathered. The level of 368 inflammatory proteins was measured using proximity extension assays. Results were validated in an independent cohort of 15 patients with scleritis, and using addressable laser bead immunoassay, or enzyme-linked immunoassays. In addition, we studied an extended panel of matrix metalloproteinases in tear fluid of necrotizing scleritis with addressable laser bead immunoassay. Main Outcome Measures: Statistically significant differences in the level of inflammatory proteins between patients with scleritis and control groups. Results: Proteomics revealed 18 significantly upregulated or downregulated serum proteins in active scleritis cases compared with all control groups in both the discovery cohort and the validation cohort. The most upregulated protein was nuclear migration protein nudC (NudC; P = 0.0032), a protein involved in neurogenesis. The other significant hits included proteins involved in T-cell activation, apoptosis, epithelial barrier maintenance, and angiogenesis. Our tear fluid analysis showed matrix metalloproteinase 9 (MMP9) to be upregulated in the tear fluid of patients with scleral necrosis. Conclusions: The results of our proteomics analysis suggest a role for neurogenesis, T-cell activation, disruption of epithelial barrier, and angiogenesis in the pathogenesis of scleritis, and highlight MMP9 and NudC as biomarkers with potential clinical relevance. Funding Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.
KW - Biomarkers
KW - Proteomics
KW - Scleritis
KW - Serum
KW - Tear fluid
UR - http://www.scopus.com/inward/record.url?scp=85177220548&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.xops.2023.100407
DO - https://doi.org/10.1016/j.xops.2023.100407
M3 - Article
C2 - 38054106
SN - 2666-9145
VL - 4
JO - Ophthalmology Science
JF - Ophthalmology Science
IS - 1
M1 - 100407
ER -