Systemic Scleroderma, Systemic Sclerosis
Conditions
Keywords
Eosinophil, Fibrosis, Systemic Scleroderma
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, ..)
Interventions
DIAGNOSTIC_TESTBlood 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
DIAGNOSTIC_TESTSkin biopsies
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)
Sponsors
GlaxoSmithKline
University Hospital, Lille
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 | — |
Countries
France
Outcome results
None listed