Oxidative Stress as a Regulatory Checkpoint in the Production of Antiphospholipid Autoantibodies: The Protective Role of NRF2 Pathway

Oxidative stress is a well-known hallmark of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. Oxidative stress may affect various signaling pathways and biological processes, promoting dysfunctional immune responses and inflammation, inducing apoptosis, deregulating autophagy and impairing mitochondrial function. The chronic oxidative stress and the dysregulation of the immune system leads to the loss of tolerance, which drives autoantibody production and inflammation with the development of endothelial dysfunction. In particular, anti-phospholipid antibodies (aPL), which target phospholipids and/or phospholipid binding proteins, mainly fi-glycoprotein I (fi-GPI), play a functional role in the cell signal transduction pathway(s), thus contributing to oxidative stress and thrombotic events. An oxidation-antioxidant imbalance may be detected in the blood of patients with APS as a reflection of disease progression. This review focuses on functional evidence highlighting the role of oxidative stress in the initiation and progression of APS. The protective role of food supplements and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) activators in APS patients will be summarized to point out the potential of these therapeutic approaches to reduce APS-related clinical complications.

Automated summary

Oxidative stress plays a crucial role in the initiation and progression of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by thrombosis and pregnancy morbidity. It affects various biological processes and signaling pathways, leading to dysfunctional immune responses, inflammation, apoptosis, autophagy deregulation, and impaired mitochondrial function. The imbalance between oxidation and antioxidant mechanisms in APS patients reflects disease progression. This review focuses on the role of oxidative stress in APS and explores potential therapeutic approaches, such as food supplements and NRF2 activators, to reduce the clinical complications associated with APS.