Clinical trial NCT04995588: Systemic Sclerosis and Innate T Cells
Official title: Role of Innate T Cells in Physiopathology of Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Sclerosis
Lead sponsor: Poitiers University Hospital
Sponsor class: OTHER
First posted: 2021-08-09
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Basal numeration of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
timeFrame: Through study completion, an average of 1 year
measure: Basal expression level of Ki67 among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
timeFrame: Through study completion, an average of 1 year
measure: Basal expression level of PLZF AND Eomes AND T-bet AND Helios of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
timeFrame: Through study completion, an average of 1 year
measure: Basal expression of perforin AND granzyme A among circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
timeFrame: Through study completion, an average of 1 year
measure: 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
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Poitiers
country: France
facility: CHU poitiers
Study officials:
References: