Role of Eosinophil in Fibrogenesis of Systemic Sclerosis

• Conditions: Systemic Scleroderma; Systemic Sclerosis
• Interventions: Diagnostic Test: Blood test; Diagnostic Test: Skin biopsies

• Registration Number: NCT03816189
• Lead Sponsor: University Hospital, Lille

Brief Summary

Eosinophils are involved in tissue remodeling and fibrosis in many inflammatory diseases. Systemic sclerosis (SSc) is an autoimmune disease with fibrotic skin and lung complications. The profibrosing properties and data from the SSc literature suggest a possible role of the eosinophils in the process of fibrogenesis of SSc.

Detailed Description

it will assess the activation state of blood eosinophils in SSc patients compared to healthy controls (ECP production in vitro, surface activation markers, whole transcriptome array, ..).

it will also study skin eosinophils and their recruitment (extracellular eosinophil granules, eotaxins production in skin, ..)

Study Timeline

• Study Start: 2018-10-03
• Study First Submitted: 2018-12-18
• Study First Submitted QC: 2019-01-21
• Study First Posted: 2019-01-25
• Status Verified: 2020-08
• Last Update Submitted: 2021-03-10
• Last Update Posted: 2021-03-11
• Primary Completion: 2021-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

• For SSc patients:
• Meeting the 2013 ACR-EULAR criteria for diffuse SSc (n = 20) and limited SSc (n = 20)
• Having signed the informed consent
• Eosinophils ≥ 0.1 G / L on the last blood test (<3 months)

For healthy subjects:

• Without chronic pathology requiring long-term treatment
• Eosinophils between 0.1 and 0.4 G / L on recent blood test (<3 months)

Exclusion Criteria for patients and controls:

• Patient with an infection, state of emergency or progressive neoplastic pathology
• Pregnant or lactating women
• History of atopy (allergic asthma, atopic eczema, allergic rhinitis, allergic conjunctivitis)
• Allergy to local anesthetics (for scleroderma patients only)
• Taking into account a minimum weight of 50 kg and in the absence of cardiorespiratory effects of scleroderma, only patients with at least 10 g of hemoglobin will be included

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Limited SSc	Blood test	Recruitment of 20 patients with limited SSc
Diffuse SSc	Blood test	Recruitment of 20 patients with diffuse SSc
Diffuse SSc	Skin biopsies	Recruitment of 20 patients with diffuse SSc
Healthy subjects	Blood test	Recruitment of 20 healthy subjects (control)
Limited SSc	Skin biopsies	Recruitment of 20 patients with limited SSc

Primary Outcome Measures

Name	Time	Method
Comparison of ECP concentrations in supernatants of eosinophils culture	Baseline: one session	Eosinophils will be sorted, stimulated in vitro for 2 hours and ECP concentration will be assessed in supernatants

Secondary Outcome Measures

Name	Time	Method
In skin biopsies: density of eosinophils, extracellular ECP and MBP deposits (absent in healthy skin), and density of eotaxin-1-producing cells will be assessed in damaged skin and apparently healthy skin of SSc patients	Baseline: one session
Comparison of median fluorescence intensities of several surface markers on blood eosinophils, or comparison of percentages of positive cells among all eosinophils for a given marker (flow cytometry)	Baseline: one session	MFI/% of CD69, HLA class II, CD9, CD11c, CD44, CCR3, CRTH2, IL-5R on blood eosinophils
Gene expression profiles will be compared between SSc patients and healthy controls (whole transcriptome assay)	Baseline: one session	Whole genome, transcriptomic approach (differentially expressed genes will be identified using a fold change cutoff)

Trial Locations

Locations (1)

Hôpital Claude Huriez, CHU; 🇫🇷 Lille, France