Neutrophil Extracellular Traps in Systemic Sclerosis

NCT ID: NCT03374618

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-23
• Study Completion Date: 2021-04-29

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.

We hypothesis that this phenomenon could be dysregulated in SSC as in SLE and could play a prominent role in the induction of autoimmunity, as well as in the induction and perpetuation of organ damages.

Detailed Description

This study is designed to assess the role of neutrophil extracellular traps (NETs) in systemic sclerosis as well as to evaluate the correlation between NETs production and NETs composition and the different complications and phenotypes observed in SSC.

30 SSC patients, 30 SLE patients and 60 healthy subjects will be recruited. Blood samples will be collected to obtain plasma, serum and polynuclear neutrophils by negative selection.

1. The main aim of the study is to evaluate the quantity of NETs induced by serum from SSc patients on neutrophils from either healthy or SSC patients in vitro. The quantity of NETs produced by different populations of neutrophils in contact with sera from SSC will be compared with those produced by the same different populations of neutrophils in contact with sera from SLE, and healthy subjects (two control populations).

2. Other objectives:

• To assess the composition of the NETs produced by different populations of neutrophils exposed to serum from SSC, SLE and healthy subjects.
• To correlate the quantity and the composition of NETS with clinical phenotype in SSc
• To assess the role of serum cytokines in Nets production in SSC.

Conditions

Systemic Lupus Erythematosus; Systemic Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

systemic lupus erythematosus

adult with systemic lupus erythematosus

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

systemic sclerosis

adult with systemic sclerosis

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

healthy volunteers

healthy volunteer (adult)

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

Interventions

Blood sample

Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

for patients of arm 1:

• patients with systemic lupus erythematosus
• patients consenting to participate to the study
• patients enrolled in the national healthcare insurance program

for patients of arm 2:

• patients with systemic sclerosis
• patients consenting to participate to the study
• patients enrolled in the national healthcare insurance program

For patients of arm 3 (healthy volunteers)

• Patients without Chronic inflammatory systemic disease
• Patients without Current or past neoplasy,
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CHU de Reims

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Damien JOLLY

Reims, , France

Countries

France

Other Identifiers

PO17014

Identifier Type: -

Identifier Source: org_study_id