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).
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: 1. 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; 2. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
90
A 51 mL blood sample will be collected during the study
If synovial aspiration is required in standard care for patients with peripheral spondylarthritis. Medical waste product will be collected for the study
Hôpital Henri-Mondor, AP-HP - Service de Rhumatologie
Créteil, France
NOT_YET_RECRUITINGHôpital Cochin, AP-HP - Department of Dermatology B
Paris, France
RECRUITINGHôpital Saint-Antoine, AP-HP - Service de Rhumatologie
Paris, France
RECRUITINGHôpital Maison Blanche - Service de Rhumatologie
Reims, France
NOT_YET_RECRUITINGProfiling of open chromatin regions
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
Time frame: 4 years
Profiling of transcriptome
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
Time frame: 4 years
Profiling of the genome
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
Time frame: 4 years
Profiling of cytokine expression
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
Time frame: 4 years
Single cell transcriptome analysis
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;
Time frame: 4 years
Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients
Define the effects in vitro of IL-23 blockade on immune responses in the peripheral blood of axSpA patients, using whole blood culture assays to profile stimulated protein secretion and gene expression, in the presence or absence of IL-23 inhibitors. As this therapy is not employed for the treatment of axSpA, we will characterize the in vitro effects of anti-IL-23 blockade on the immune responses of patients with axSpA, by analysing gene expression and protein secretion in whole blood cultures in the presence or absence of anti-IL-23 treatment. We will isolate MAIT, γδ TCR+, CD4+CCR6+ and CD8+CCR6+ (enriched in IL-23R+) T cell populations from peripheral blood of psoriasis patients and stimulate them through the T cell receptor (TCR), in the presence or absence of IL-23.
Time frame: 4 years
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