Systemic Sclerosis and Innate T Cells

Systemic Sclerosis Clinical Trial

Official title:

Role of Innate T Cells in Physiopathology of Systemic Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04995588
• Other study ID #: Sclero-LTI
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2022
• Est. completion date: January 28, 2026

Study information

• Verified date: September 2023
• Source: Poitiers University Hospital
• Contact: Mickaël MARTIN, MD, PhD
• Phone: +33549444004
• Email: mickael.martin[@]chu-poitiers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: January 28, 2026
• Est. primary completion date: August 28, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Other:
• Blood test
Unique blood draw of 45mL for all the participants

Locations

Country	Name	City	State
France	CHU poitiers	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
Poitiers University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Basal numeration of circulating ITC (iNKT, MAIT, ?d-T and innate CD8(+) T-cells)	Percentage AND absolute count of iNKT, MAIT, ?d-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
Primary	Basal expression level of Ki67 among circulating ITC (iNKT, MAIT, ?d-T and innate CD8(+) T-cells)	Percentage of iNKT, MAIT, ?d-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
Primary	Basal expression level of PLZF AND Eomes AND T-bet AND Helios of circulating ITC (iNKT, MAIT, ?d-T and innate CD8(+) T-cells)	Percentage of iNKT, MAIT, ?d-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
Primary	Basal expression of perforin AND granzyme A among circulating ITC (iNKT, MAIT, ?d-T and innate CD8(+) T-cells)	Percentage of iNKT, MAIT, ?d-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
Primary	IFN-?, IL-4 and IL-17 production of iNKT, MAIT, ?d-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, ?d-T and innate CD8(+) T-cells expressing IFN-? 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