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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitut Pasteur

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Blood sampling

    Other intervention

    A 51 mL blood sample will be collected during the study

  • synovial aspiration

    Other intervention

    If synovial aspiration is required in standard care for patients with peripheral spondylarthritis. Medical waste product will be collected for the study

Treatment groups

90 Participants
are divided into 2 treatment groups
Group A: Patients with axial spondyloarthritis participating in the studyExperimental treatment 1 intervention
Group B: Patients with peripheral spondyloarthritis participating in the studyExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Profiling 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
2

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
3

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
4

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

Secondary outcomes

1

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

Other outcomes

Sponsors and contacts

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Institut Pasteur

Lead sponsor

Janssen Biotech, Inc.

Collaborator