Systemic Sclerosis and Innate T Cells

Study Overview
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Brief Summary
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Innate T cells (ITC) are decreased in systemic sclerosis (SS) and an early lymphocyte innateness has been reported. In the other part, ITC are implicated on inflammatory process, including the IL-33/ST2 axis, which is also involved in ScS endotheliopathy. Data are however scarce and physiopathological mechanisms have not been assessed to date. The investigators hypothesize a global lymphocyte innateness in SSc, linked to a chronic ITC stimulation by innate signals leading to ITC exhaustion, and their potential role in endotheliopathy and fibroblast activation in SSc.

Official Title
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Role of Innate T Cells in Physiopathology of Systemic Sclerosis

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Other: Blood test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SSc according to the 2013 ACR/EULAR 2013 criteria (or the 2001 Leroy's criteria for early SSc) Patients with others connective tissue disease: Systemic erythematosus lupus (SLE) according to the 2019 ACR/EULAR criteria Primary Sjögren syndrome (pSS) according to the 2016 ACR/EULAR criteria Rheumatoid arthritis according to the 2010 ACR/EULAR criteria Idiopathic inflammatory myopathy (IIM) according to the 2017 ACR/EULAR criteria Healthy subjects from general population without known autoimmune disease or connective tissue disease ≥18 years-old Exclusion Criteria: Overlap syndrome (including secondary Sjögren syndrome) Weight <55 kgs Known primary cell immunodeficiency Past of autologous or allogenic hematopoietic stem cell transplantation Solid neoplasia or malignant hemopathy in remission for less than 12 months an Chemotherapy and/or immune checkpoint inhibitors in the last 12 months Systemic retinoids Active infection and/or antibiotics in the last 2 weeks Known active chronic infection among HIV, HTLV, viral hepatitis, syphilis Vaccination in the last 4 weeks Subject refusing genetic analysis for the present study Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Blood test<br>Unique blood test for all the participants included in the study to constitute a local biobank to assess in a grouped manner the prespecified outcomes | Other: Blood test<br>* Unique blood draw of 45mL for all the participants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basal numeration of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) | Percentage AND absolute count of iNKT, MAIT, γδ-T and innate CD8(+) T- cells in flow cytometry among total T cells in SSc patients (n=60), patients with other connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, idiopathic inflammatory myopathies) (n=60), and in healthy subjects (n=60) | Through study completion, an average of 1 year | 
| Basal expression level of Ki67 among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) | Percentage of iNKT, MAIT, γδ-T and innate CD8(+) T-cells expressing Ki67 in flow cytometry in SSc patients (n=60), patients with other connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, idiopathic inflammatory myopathies) (n=60), and in healthy subjects (n=60) | Through study completion, an average of 1 year | 
| Basal expression level of PLZF AND Eomes AND T-bet AND Helios of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) | Percentage of iNKT, MAIT, γδ-T and innate CD8(+) T-cells expressing PLZF, Eomes, T-bet and Helios in flow cytometry in SSc patients (n=60), patients with other connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, idiopathic inflammatory myopathies) (n=60), and in healthy subjects (n=60) | Through study completion, an average of 1 year | 
| Basal expression of perforin AND granzyme A among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) | Percentage of iNKT, MAIT, γδ-T and innate CD8(+) T-cells expressing perforin and granzyme A in flow cytometry in SSc patients (n=60), patients with other connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, idiopathic inflammatory myopathies) (n=60), and in healthy subjects (n=60) | Through study completion, an average of 1 year | 
| IFN-ɣ, IL-4 and IL-17 production of iNKT, MAIT, γδ-T and innate CD8(+) T-cells in response to IL-1, IL-8, IL-12, IL-18, IL-33 and fractalkine | Percentage of iNKT, MAIT, γδ-T and innate CD8(+) T-cells expressing IFN-ɣ AND IL-4 AND IL-17 in flow cytometry upon stimulation by various combinations of IL-1, IL-8, IL-12, IL-18, IL-33 and fractalkine in SSc patients (n=60), patients with other connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, idiopathic inflammatory myopathies) (n=60), and in healthy subjects (n=60) | Through study completion, an average of 1 year |