Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage. The redox status of neutrophils sourced from synovial fluid (SF) was measured by flow cytometry in terms of total ROS and hydroxyl radicals. Among the molecular damage markers, protein carbonylation and lipid peroxidation were detected by spectrophotometry and S-nitrosothiols by fluorimetry. Neutrophils constituted the major cellular component of the SF of patients with RA and their levels of ROS and hydroxyl radicals correlated strongly with protein carbonylation and lipid peroxidation. However, all the oxidative damage markers correlated positively with DAS28. Taken together, in patients with RA, the strong correlation between levels of ROS and DAS28 with markers of oxidative damage suggests that measurement of oxidative stress could serve as a biomarker for monitoring disease severity in RA.