Potential Biomarkers for Noninfectious Scleritis Identified by Serum and Tear Fluid Proteomics
Ophthalmology Science, 2023
Vergouwen D., Kolijn P., de Hoog J., de Boer J., Los L., Gijs M., Erckens R., de Jong P., Rothova A., Ten Berge J., Schreurs M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Ophthalmology | Pathophysiology Patient Stratification | Serum Tear Fluid |  Olink Explore 3072/384 |
Abstract
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 non-infectious scleritis (of which 39 active cases), 30 healthy controls, and 23 disease controls (uveitis and rheumatoid arthritis) were enrolled in the Netherlands from 2020 – 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 scleritis patients, and using addressable laser bead immunoassay (ALBIA), or enzyme linked immunoassays. In addition, we studied an extended panel of matrix metalloproteinases in tear fluid of necrotizing scleritis with ALBIA.
Main outcome measures
Statistically significant differences in the level of inflammatory proteins between patients with scleritis and control groups.
Results
Proteomics revealed 18 significantly up- or downregulated serum proteins in active scleritis cases compared to 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