Role of Eosinophil in Fibrogenesis of Systemic Sclerosis

University Hospital, Lille70 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Systemic Sclerosis Systemic Scleroderma

Interventions

Blood testDIAGNOSTIC_TEST

Patients in each group will have a blood sample (9x7 mL) for eosinophils isolation, study of activation markers on whole blood and serum biomarkers testing

Skin biopsiesDIAGNOSTIC_TEST

In patients who will accept, skin biopsies will be performed in damaged and apparently normal skin, excluding fingers, hands, feet and face (biopsies are facultative)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 66 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Hôpital Claude Huriez, CHU

Lille, France

Outcomes

Primary Outcomes

Comparison of ECP concentrations in supernatants of eosinophils culture

Eosinophils will be sorted, stimulated in vitro for 2 hours and ECP concentration will be assessed in supernatants

Time frame: Baseline: one session

Secondary Outcomes

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)

MFI/% of CD69, HLA class II, CD9, CD11c, CD44, CCR3, CRTH2, IL-5R on blood eosinophils

Time frame: Baseline: one session

Gene expression profiles will be compared between SSc patients and healthy controls (whole transcriptome assay)

Whole genome, transcriptomic approach (differentially expressed genes will be identified using a fold change cutoff)

Time frame: Baseline: one session

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

Time frame: Baseline: one session

Data from ClinicalTrials.gov

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