The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Profiling of open chromatin regions
研究概览
简要总结
This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a multicentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in Spondyloarthritis patients attending the rheumatology department of Cochin, Saint-Antoine, Henri-Mondor hospitals (APHP) and Maison-Blanche Hospital (Reims).
详细描述
The aim of this project is to improve our understanding of the role of IL-23 in the pathophysiology of axial SpA and peripheral SpA.
This objective is detailed in three specific aims:
- Define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype;
- Phenotypically characterize immune cell populations in peripheral blood and in synovial fluid from peripheral SpA patients and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17.
The study population to be included are patients affected by SpA, attended to in the Rheumatology Departments of Cochin Hospital, Saint-Antoine Hospital Henri-Mondor hospitals in Paris (APHP) and Maison-Blanche Hospital in Reims. Participants will be divided into two groups: Group 1 comprises patients diagnosed with axial SpA, Group 2 SpA patients with peripheral SpA or psoriatic arthritis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- 否
入选标准
- •Age : Adults (>18 years)
- •Satisfying ASAS diagnostic criteria for SpA
- •Patient has active disease, defined by the presence of active synovitis, tendinitis, or dactylitis or significant inflammatory pain of the spine, judged by the examining clinician to be due to SpA.
- •Informed consent signed
- •Beneficiary of health insurance, except for the AME
- •Only for patients of Group 1 • Patient is naïve to biological therapies
- •Only for patients of Group 2
- •Patient is affected by peripheral SpA (ASAS criteria) or psoriatic arthritis, with inflammation of peripheral joints
- •Patient requires aspiration, as part of standard care
- •Non inclusion criteria:
- •Patient is minor
- •Patient is pregnant or breastfeeding
- •Patient is immunocompromised
- •Patient has received biological therapy with 2 or more biologics
- •Patient is receiving corticosteroid treatment > 10 mg per day
- •Patient is under legal protection, curators, guardianship
- •Patient refuses consent
- •Previous history of alcoholism, drug addiction, psychological problems, severe concomitant conditions that could invalidate the patient's consent or limit the patient's compliance to the treatment protocol.
- •Beneficiary of the AME
- •Only for group 1
- •Patient has received biological therapy
排除标准
- 未提供
结局指标
主要结局
Profiling of open chromatin regions
时间窗: 4 years
Profiling of open chromatin regions (ATAC seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype
Profiling of transcriptome
时间窗: 4 years
Profiling of the transcriptome (RNA-seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype
Profiling of cytokine expression
时间窗: 4 years
Profiling of cytokine expression (Proximity Extension Assay technology) in T lymphocytes, cultured in the presence or absence of IL-23 in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype
Single cell transcriptome analysis
时间窗: 4 years
Single cell transcriptome analysis of cells from patients with peripheral SpA will be performed to characterize immune cell populations in peripheral blood and in synovial fluid and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17;
Profiling of the genome
时间窗: 4 years
Profiling of the genome (genotyping) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype
次要结局
- Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients(4 years)