Systemic Sclerosis and Innate T Cells

Not Applicable

Recruiting

• Conditions: Systemic Sclerosis
• Interventions: Other: Blood test

• Registration Number: NCT04995588
• Lead Sponsor: Poitiers University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-23
• Study First Submitted QC: 2021-07-29
• Study First Posted: 2021-08-09
• Study Start: 2022-02-28
• Status Verified: 2023-09
• Last Update Submitted: 2024-06-07
• Last Update Posted: 2024-06-10
• Primary Completion: 2025-08-28
• Study Completion: 2026-01-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Blood test	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

Primary Outcome Measures

Name	Time	Method
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 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)
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)
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 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)

Trial Locations

Locations (1)

CHU poitiers; 🇫🇷 Poitiers, France