Neutrophil Extracellular Traps in Different Forms of Systemic Sclerosis

Recruiting

• Conditions: Systemic Sclerosis; Other Connective Tissue Disease; Systemic Lupus Erythematosus; Dermatomyositis; ANCA Associated Vasculitis
• Interventions: Other: Blood sample

• Registration Number: NCT06462768
• Lead Sponsor: CHU de Reims

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2023-11-27
• Status Verified: 2024-06
• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-06-12
• Last Update Submitted: 2024-06-12
• Study First Posted: 2024-06-17
• Last Update Posted: 2024-06-17
• Primary Completion: 2028-10-27
• Study Completion: 2029-04-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

*For patients of group 1:

• Patients with systemic sclerosis (ACR-EULAR Criteria)
• Patients taking care of in internal medicine or in dermatology department's of the university hospital of Reims
• Patients consenting to participate to the study
• Patients enrolled in the national healthcare insurance program

For patients of group 2:

• Patients with other connective tissue disease (ACR specific-disease criteria)
• Patients taking care of in internal medicine or in dermatology department's of the university hospital of Reims
• Patients consenting to participate to the study
• Patients enrolled in the national healthcare insurance program

For patients of group 3 (healthy volunteers)

• Patients eligible for blood donation (blood donation regulation criteria of January 11th 2022 decree)
• Patients without medical history of autoimmune systemic or chronic inflammatory systemic disease,
• Patients without current or past neoplasy disease,
• Patients without chronic metabolic pathology
• Patients without treatment by anti inflammatory or corticotherapy for the last 15 days,
• Patients without infectious pathology or inflammatory acute for the last 15 days
• Patients consenting to participate to the study

Exclusion Criteria for patients of all groups:

• Patients/Healthy volunteers under 18 years old
• Patients/Healthy volunteers protected by the law
• Patients/Healthy volunteers not consenting to participate to the study after information
• Patients with inflammatory pathology or infectious acute intercurrent pathology in the last 15 days before inclusion
• Pregnant or breastfeeding women

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	Blood sample	Healthy adult volunteer
Adult with SSc	Blood sample	Adult with SSc
Other connective tissue disease	Blood sample	Adult with other connective tissue disease

Primary Outcome Measures

Name	Time	Method
Quantification of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls.	Day 0	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.

Secondary Outcome Measures

Name	Time	Method
Analysis of the composition of Neutrophil Extracellular Traps (NETs)	Day 0	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.
Analysis of the cytokines influencing Neutrophil Extracellular Traps NETs production in vitro	Day 0	Comparative analysis of the quantity of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils from SSC patients in vitro by differents cytokines

Trial Locations

Locations (1)

Chu Reims; 🇫🇷 Reims, France