Abstract: 3-Nitrotyrosine (3-NT) is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It serves as an indicator of inflammation, cell damage, and nitric oxide production. Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by multisystem involvement and increased oxidative stress. Notably, cardiovascular (CV) disease has emerged as the leading cause of mortality among SLE patients. Our objective was to investigate the association between serum 3-NT levels and a wide range of disease characteristics in patients with SLE, with a particular emphasis on CV comorbidity. A total of 214 patients with SLE were enrolled. The serum levels of 3-NT as well as the activity (SLEDAI) and damage index (SLICC-SDI) scores, full lipid profile, insulin resistance indices, and carotid subclinical atherosclerosis were assessed. Multivariable linear regression analysis was carried out to study the relationship between 3-NT and clinical and laboratory disease characteristics, especially focusing on CV comorbidities. Except for body mass index, which showed a significant positive correlation, the demographic data and traditional CV risk factors did not correlate with 3-NT. After multivariable adjustments, several disease characteristics, including the disease duration, activity and damage indices, and autoantibody profile, showed significant positive associations with 3-NT. Regarding CV characteristics, several lipid profile molecules showed significant relationships with 3-NT. This was not the case for insulin resistance and subclinical atherosclerosis. Remarkably, patients with a high CV risk by SCORE2 showed higher 3-NT values compared to those with a low risk, although after the multivariable adjustment, this relationship was attenuated (but still showed a trend). In conclusion, serum 3-NT levels demonstrated significant positive correlations with multiple disease characteristics, including the disease activity and damage and the autoantibody profile. The lipid pattern in the SLE subjects also significantly and independently correlated with the 3-NT values. Our findings highlight the pathophysiological role of 3-NT specifically, and peroxidation in general, in patients with SLE.

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