Systemic Sclerosis and Innate T Cells

Role of Innate T Cells in Physiopathology of Systemic Sclerosis

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.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Other: Blood test

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Poitiers, France
    • CHU Poitiers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): December 12, 2025
• Study Completion (Actual): December 17, 2025

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests
• Other Study ID Numbers: Sclero-LTI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No