Systemic Sclerosis
Conditions
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.
Interventions
OTHERBlood test
Unique blood draw of 45mL for all the participants
Sponsors
Poitiers University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
France
Outcome results
None listed