The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis

Not Applicable

Recruiting

• Conditions: Spondyloarthritis
• Interventions: Other: Blood sampling; Other: synovial aspiration

• Registration Number: NCT05290363
• Lead Sponsor: Institut Pasteur

Brief Summary

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).

Detailed Description

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 Timeline

• Study First Submitted: 2022-02-25
• Study First Submitted QC: 2022-03-11
• Study First Posted: 2022-03-22
• Study Start: 2022-10-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-23
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• 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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with peripheral spondyloarthritis participating in the study	Blood sampling	People with peripheral spondylarthritis (30 participants).
Patients with axial spondyloarthritis participating in the study	Blood sampling	People with axial spondylarthritis (60 participants),
Patients with peripheral spondyloarthritis participating in the study	synovial aspiration	People with peripheral spondylarthritis (30 participants).

Primary Outcome Measures

Name	Time	Method
Profiling of open chromatin regions	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	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	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	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	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

Secondary Outcome Measures

Name	Time	Method
Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients	4 years	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.

Trial Locations

Locations (4)

Hôpital Henri-Mondor, AP-HP - Service de Rhumatologie; 🇫🇷 Créteil, France

Hôpital Cochin, AP-HP - Department of Dermatology B; 🇫🇷 Paris, France

Hôpital Saint-Antoine, AP-HP - Service de Rhumatologie; 🇫🇷 Paris, France

Hôpital Maison Blanche - Service de Rhumatologie; 🇫🇷 Reims, France