Systemic Sclerosis and Innate T Cells
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Blood test 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
Unique blood draw of 45mL for all the participants
|
Outcome Measures
Primary Outcome Measures
- Basal numeration of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) [Through study completion, an average of 1 year]
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)
- Basal expression level of Ki67 among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) [Through study completion, an average of 1 year]
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)
- Basal expression level of PLZF AND Eomes AND T-bet AND Helios of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) [Through study completion, an average of 1 year]
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)
- Basal expression of perforin AND granzyme A among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells) [Through study completion, an average of 1 year]
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)
- 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 [Through study completion, an average of 1 year]
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)
Eligibility Criteria
Criteria
Inclusion Criteria:
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SSc according to the 2013 ACR/EULAR 2013 criteria (or the 2001 Leroy's criteria for early SSc)
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Patients with others connective tissue disease:
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Systemic erythematosus lupus (SLE) according to the 2019 ACR/EULAR criteria
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Primary Sjögren syndrome (pSS) according to the 2016 ACR/EULAR criteria
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Rheumatoid arthritis according to the 2010 ACR/EULAR criteria
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Idiopathic inflammatory myopathy (IIM) according to the 2017 ACR/EULAR criteria
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Healthy subjects from general population without known autoimmune disease or connective tissue disease
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≥18 years-old
Exclusion Criteria:
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Overlap syndrome (including secondary Sjögren syndrome)
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Weight <55 kgs
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Known primary cell immunodeficiency
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Immunosuppressive drug in the past 3 months (hydroxychloroquine and glucocorticoids ≤7.5mg/d allowed)
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Biotherapy in the past 6 months
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Past of autologous or allogenic hematopoietic stem cell transplantation
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Solid neoplasia or malignant hemopathy in remission for less than 12 months an
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Chemotherapy and/or immune checkpoint inhibitors in the last 12 months
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Systemic retinoids
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Active infection and/or antibiotics in the last 2 weeks
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Known active chronic infection among HIV, HTLV, viral hepatitis, syphilis
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Vaccination in the last 4 weeks
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Subject refusing genetic analysis for the present study
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Pregnancy or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU poitiers | Poitiers | France |
Sponsors and Collaborators
- Poitiers University Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Sclero-LTI