Relationship of serum 3-nitrotyrosine levels with inflammation in patients with rheumatoid arthritis

Abstract

Objective: 3-Nitrotyrosine (3-NT) is a byproduct of tyrosine nitration, mediated by reactive nitrogen species such as peroxynitrite and nitrogen dioxide. It serves as a marker of cellular damage, inflammation, and nitric oxide activity. Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by systemic involvement and increased oxidative stress. In RA patients, cardiovascular disease has emerged as the leading cause of mortality. This study aimed to investigate the relationship between serum 3-NT levels and various disease characteristics in RA patients, with a particular focus on cardiovascular comorbidities. Methods: A total of 168 RA patients were recruited. They underwent comprehensive evaluations, including disease-related characteristics and disease activity indices. Furthermore, a comprehensive lipid panel, measures of insulin resistance, metabolic syndrome criteria, and carotid ultrasound to evaluate intima-media thickness and the presence of carotid plaques were conducted. 3-NT serum levels were measured. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and 3-NT. Results: After multivariable analysis, C-reactive protein was independently associated with higher serum levels of 3-NT. In contrast, disease characteristics and Disease Activity Score 28-joint count (DAS28) calculated using C-reactive protein or erythrocyte sedimentation rate, showed no significant association with 3-NT levels. Likewise, cardiovascular comorbidities, including lipid profiles, insulin resistance indices, metabolic syndrome, and markers of subclinical atherosclerosis did not demonstrate any significant relationship with 3-NT levels. Conclusions: While 3-NT levels are influenced by inflammation, they do not appear to be strongly associated with disease characteristics, cardiovascular risk, or disease-modifying anti-rheumatic drugs in RA patients. This emphasizes the complexity of oxidative stress in RA.