A study published in Arthritis & Rheumatology clarifies, through clinical, tissue and laboratory data, why the risk of cardiovascular events is so high in systemic lupus erythematosus (SLE). The research was carried out in collaboration between Giacomo Emmi, immunologist and Professor of Internal Medicine at the University of Trieste, and the research teams of Matteo Becatti, Claudia Fiorillo and Domenico Prisco at the University of Florence.

SLE is a systemic autoimmune disease that can affect several organs. In Italy it affects more than 60,000 people, mostly women of childbearing age. For those affected, the risk of arterial and venous thrombosis can be two to ten times higher than in the general population. The underlying cause is not limited to cholesterol or blood pressure, but primarily linked to the chronic inflammation characteristic of the disease.

At the centre of this process is oxidative stress, the imbalance between oxidising substances produced by our cells and the antioxidant defences that should neutralise them. In SLE patients, certain immune cells – neutrophils – are abnormally active and fuel this imbalance. In such an oxidative environment, fibrinogen, the protein forming the network of the blood clot, behaves differently: the fibres become denser and less permeable, and the clots harder to dissolve. This mechanism directly connects inflammation to thrombotic risk.

The study involved 144 adult SLE patients and 90 healthy controls. Blood analyses documented higher oxidative stress in patients and its correlation with disease activity. Tissue observations confirmed the picture: in renal biopsies from individuals with active lupus nephritis (inflammation of the kidneys), the same mechanism was evident precisely where inflammation was most intense, demonstrating that it is not only a circulating phenomenon but also causes damage at the organ level.

To confirm the causal link, the team reproduced the phenomenon in the laboratory. When fibrinogen was exposed to an oxidative environment, the clots became more compact and resistant; when a reference antioxidant was added, the effect disappeared. The sequence is thus clear: more inflammation → more oxidative stress → altered fibrinogen → clots harder to dissolve.

‘These results provide a deeper understanding of the connection between autoimmune disease and cardiovascular complications,’ says Professor Giacomo Emmi, who teaches at the Department of Medicine, Surgery and Health Sciences of the University of Trieste and is Head of the Clinical Medicine Unit and Scientific Coordinator of the local health authority (ASUGI).

‘Oxidative stress,’ explains Emmi, ‘emerges as a new potential therapeutic target. Alongside the management of traditional risk factors and disease activity, future therapies could aim to modulate these oxidative circuits to more effectively protect the heart and blood vessels of patients with lupus.’

Reference: ROS-induced modifications of fibrin clots connect immune responses to atherothrombosis in systemic lupus erythematosus, in Arthritis & Rheumatology. DOI: 10.1002/art.43371.