Role of Innate T Cells in Physiopathology of Systemic Sclerosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 235
- 试验地点
- 1
- 主要终点
- Basal numeration of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Blood test (Other)
结局指标
主要结局
Basal numeration of circulating ITC (iNKT, MAIT, γδ-T and innate CD8(+) T-cells)
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
次要结局
未报告次要终点