Tear Fluid Protein Changes in Dry Eye Syndrome Associated with Rheumatoid Arthritis: A Proteomic Approach

Abstract

Purpose: Sjögren syndrome (SS) secondary to rheumatoid arthritis (RA) affects lacrimal and salivary glands, and therefore dry eye syndrome (DES) is more prevalent in patients with RA. This study used a proteomic approach to identify potential biomarkers in tear of DES secondary to RA (DES-RA).

Methods: Tear specimens were collected with Schirmer strips from patients with DES with RA, patients with other types of dry eye (namely, primary Sjögrens and non-Sjögrens [NSS]), and age-matched controls. Tear proteins were subjected to 2D-differential gel electrophoresis (2D-DIGE), and the differentially expressed proteins were identified using nano ESI-LC-MS/MS analysis.

Results: Among the differentially regulated proteins of DES-RA that were identified, lactotransferrin isoform 1 precursor was found to be d own-regulated in 100% cases and SHC transforming 1 isoform in 63% of the cases, while proteins such as ribonuclease p protein subunit 20, protocadherin, and heterogeneous nuclear ribonucleoprotein Q isoform 6 were down-regulated in over 80% of the cases. Proteins such as Ecto-ADP ribosyltransferase 5 precursor, Rho-related GTP-binding protein, and RhoJ precursor were up-regulated in 80% of the cases.

Conclusion: Functional annotation revealed that these proteins have roles in regulation, antimicrobial activity, immune, metabolic, and cellular processes. The study observed characteristic marker proteins differentially expressed in DES-RA that are previously unreported. Further validation is needed.

Keywords: 2D-DIGE; Sjögren syndrome; clinical proteomics; dry eye syndrome; mass spectrometry; rheumatoid arthritis; tear proteomics.