Neutrophil Extracellular Traps in Different Forms of Systemic Sclerosis

Systemic SClerosis (SSC) is a systemic disease characterized by limited or diffuse cutaneous sclerosis, microangiopathy, overproduction of autoantibodies and variable organ damage due to vasculopathy and/or fibrosis. The loss of self-tolerance is believed to be caused by the dysregulation of both innate and adaptive immune systems and may involve Reactive Oxygen Species (ROS). Neutrophils are potent producers of ROS and may play a role in endothelial cells and fibrobasts dysfunction, as in autoantibodies generation. However, their role in SSC pathogenesis remains to be determined. Recent studies discovered abnormal regulation of Neutrophil Extracellular Traps (NETs) in other auto-immune diseases such as Systemic Lupus Erythematosus (SLE). NETs are web-like structures composed of chromatin backbones and granular molecules. They are released by activated neutrophils through a process called "NETosis". Nets were first described in 2004 as a novel host defense mechanism to trap and kill foreign pathogens. Recent evidence shows that NETs also participate in the pathogenesis of a variety of inflammatory and autoimmune diseases, including SLE. The investigators recently highlighted this phenomenon in SSc, especially in patients with vascular complications and/or at a early stage of the disease. The investigators will now explore the factors implicated in this dysregulation of NETosis in SSc.

This study is designed to assess the role of Neutrophil Extracellular Traps (NETs) in Systemic SClerosis (SSC) as well as to evaluate the correlation between NETs production and NETs composition and the different complications and phenotypes observed in SSC. 100 SSC patients, 30 other connective tissue disease patients and 130 healthy subjects will be recruited. Blood samples will be collected to obtain plasma, serum and polynuclear neutrophils by negative selection.