Introduction: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterised by dysregulation of the immune system, production of self-reactive antibodies and an inflammatory state in organs and tissues. Oxidative stress has been implicated in the pathogenesis of cardiovascular events in SLE, promoting tissue injury and inflammation. Thrombosis is a well-known clinical feature in SLE but, despite the large number of risk factors, its underlying pathogenetic mechanisms are far to be understood. This study aimed to explore how oxidative changes in the structure and function of fibrinogen may contribute to the development of atherothrombosis in SLE.

Methods: Here, we recruited 144 adult SLE patients and 90 non-SLE controls. We assayed systemic redox status and, in purified fibrinogen fractions, we explored fibrinogen functional and structural features.

Results: Compared to the control group, SLE patients showed higher leukocyte ROS production. This increase was accompanied by higher plasma lipid peroxidation, decreased antioxidant defenses, and increased fibrinogen oxidation. Additionally, SLE patients displayed significant fibrinogen structural alterations and changes in blood clot architecture, characterized by lower porosity and a denser fibrin network with thinner fibrin fibers. Notably, functional properties of fibrinogen, such as thrombin-induced fibrin polymerization and susceptibility to plasmin-induced lysis, were more markedly affected in SLE patients than in controls. These structural and functional fibrinogen changes strongly correlated with redox parameters, which were also associated with SLE disease activity.

Conclusions: These data suggest that, in SLE patients, ROS induce structural and functional changes in fibrinogen. This could represent a new pathogenetic mechanism underlying atherothrombosis in SLE.