Tear Proteomics Approach to Distinguishing Primary from Secondary Sjögren’s Syndrome for Dry Eye Patients with Long-Term Instillation of Eyedrops

Abstract

The diagnosis and monitoring of Sjögren syndrome (SS) is often difficult, requiring a multidisciplinary approach with invasive procedures. Our aim is to elucidate the tear protein alterations of dry eye disease (DED) with primary SS (pSS) and secondary SS (sSS) with the long-term instillation of eyedrops. We collected clinical demographics and tear fluid (TF) samples from DED patients with no autoimmune diseases (non-SS-DED), pSS-DED, and sSS-DED patients, followed by TF screening with tandem mass tagging-labeling gel-free proteomics assay. Bioinformatic analysis via Ingenuity Pathway Analysis was used to identify functional pathways and interacting networks. Validation of candidate proteins with enzyme-linked immunosorbent assay on the tear samples was done. The top functional pathways of the two comparisons (sSS-DED vs. pSS-DED and sSS-DED vs. non-SS-DED) were both associated with inflammation and stress-related signaling. After constructing an interaction network model with the selected candidate proteins, five proteins were identified. A Disintegrin and Metalloproteinase domain-containing protein 10 (ADAM10) was found to be an important candidate biomarker in all groups, followed by epidermal growth factor (EGF) in TF. This study revealed novel DED markers, ADAM10 and EGF, in differentiating between primary and secondary SS patients from tears by in-depth proteomic analysis.

Advances in Sjögren’s Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms

“…Another potential candidate biomarker for SS diagnosis is A Desintegrin and Metalloproteinase domain-containing protein 10 (ADAM10). In a 2022 study, ADAM10 was found for the first time to be significantly increased in SS patients compared to non-SS patients [72].…”

“…Tear proteomic analysis has gained popularity as a diagnostic method for SS via biomarker investigation, as tears can be collected in a non-invasive manner, allowing for easy identification of ocular surface biomarkers [72].…”

Comparing Tear Film Viscosity between Sjögren and Non-Sjögren Dry Eye Disease

“…The masked technicians interpreted the examination procedure for the subject before each tear film test. After completing a dry eye questionnaire with Ocular Surface Disease Index (OSDI) [24], each subject received a series of ocular surface examinations with the K5M, including TMH [25][26][27][28][29], TFV [15,16,30,31], ocular surface redness [26,28,29,32], NIKBUT [25][26][27][28][29], and meibography [27,28,33]. Finally, each subject received cobalt blue light illuminated corneal photography after fluorescence dye staining to determine the corneal epitheliopathy [28,29,34].…”

Discovery and Verification of Sjögren’s Syndrome Protein Biomarkers in Tears by Targeted LC-MRM

“…Over the past 15 years, a few reports have involved the analysis of tear proteins in SS-DED patients using untargeted LC-MS approaches for their identification and relative quantitation. ,− From these studies, many potential disease biomarkers have been proposed based on the analysis of one cohort of patients. The screening and diagnosis of SS remain challenging, and the etiology of the disease is still not well established.…”