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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adult with SSc | Adult with SSc |
| |
| Other connective tissue disease | Adult with other connective tissue disease |
| |
| Control | Healthy adult volunteer |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood sample | Other | Blood sample to quantify and qualify NETosis in vivo and ex vivo after different stimulations. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls. | Comparative analysis of the quantity of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, other connective tissue diseases and healthy controls. Neutrophils from SSC, other connective tissue diseases and healthy subjects will be used. | Day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of the composition of Neutrophil Extracellular Traps (NETs) | Comparative analysis of the composition of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, other connective tissue diseases and healthy controls. Neutrophils from SSC, other connective tissue diseases and healthy subjects will be used. | Day 0 |
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Inclusion Criteria:
*For patients of group 1:
For patients of group 2:
For patients of group 3 (healthy volunteers)
Exclusion Criteria for patients of all groups:
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Group 1 : Adult with SSc Group 2 : Adult with other connective tissue disease Group 3 : Healthy adult volunteer
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kevin DIDIER, Dr. | Contact | 03.26.83.24.44 | kdidier@chu-reims.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chu Reims | Recruiting | Reims | 51092 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32645862 | Background | Didier K, Giusti D, Le Jan S, Terryn C, Muller C, Pham BN, Le Naour R, Antonicelli FD, Servettaz A. Neutrophil Extracellular Traps Generation Relates with Early Stage and Vascular Complications in Systemic Sclerosis. J Clin Med. 2020 Jul 7;9(7):2136. doi: 10.3390/jcm9072136. |
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| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| D008180 | Lupus Erythematosus, Systemic |
| D003882 | Dermatomyositis |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
| D001327 | Autoimmune Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Analysis of the cytokines influencing Neutrophil Extracellular Traps NETs production in vitro | Comparative analysis of the quantity of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils from SSC patients in vitro by differents cytokines | Day 0 |
| D007154 | Immune System Diseases |
| D017285 | Polymyositis |
| D009220 | Myositis |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |