This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a monocentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in psoriasis patients attending the dermatology department of hospital Cochin (APHP).
The aim of this project is to study the cellular and molecular mechanisms in patients receiving anti-IL-23 biologics as treatment for cutaneous psoriasis, in order to improve the understanding of the role of IL-23/IL-17 axis in this pathology. 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 in patients with skin psoriasis and correlate it with the patient's genotype * Identify at the single cell level the cells expressing IL-23R and/or producing IL-17 in the skin of patients with skin psoriasis; * Characterize the in vivo effects of anti-IL-23 therapy on the immune responses of patients with skin psoriasis, by analysing gene expression and protein secretion in whole blood cultures before and after treatment; The secondary objective of this study is to identify mechanisms of non-response to anti-IL-23 therapy in cutaneous psoriasis patients. The study population to be included are patients affected by cutaneous psoriasis, requiring systemic biological treatment and attended to in the Dermatology Department of the Cochin Hospital. Patients will be divided into two groups: Group 1 patients will participate once before initiation of therapy, Group 2 will participate before and after initiation of anti-IL-23 biologic treatment. Group 1: 10 patients with cutaneous psoriasis for the phenotypic and transcriptional analyses of T cell populations in peripheral blood. These patients will be sampled once before initiation of biotherapy. \- Group 2: 80 patients with a medical decision to treat cutaneous psoriasis with an anti-IL-23 biologic. These patients will be sampled twice (before and after initiation of therapy), for the analysis of blood immune cell populations using spectral flow cytometry, and immune responses using whole blood cultures. Skin biopsies will be obtained from a subset of 30 patients to analyse the skin transcriptome, before and after treatment with anti-IL-23 biologics.
Study Type
OBSERVATIONAL
Enrollment
90
Blood will be collected in tubes heparinés BD (Vacutainer), homogenised, and immediately transported at room temperature to Institut Pasteur to be further processed
collection of socio-demographic, clinical and biological data.
skin biopsies of 4 mm in diameter. These samples will not be taken on the face or in an area of skin folds
Lars ROGGE
Paris, Île-de-France Region, France
RECRUITINGProfiling of open chromatin regions
Profiling of open chromatin regions (ATAC seq), of the transcriptome (RNA-seq), of the genome (genotyping), and of cytokine expression (Luminex technology) in T lymphocytes from patients with cutaneous psoriasis, untreated or treated with IL-23 in vitro
Time frame: 7 years
Single cell transcriptome analysis
Single cell transcriptome analysis of skin biopsies from patients with cutaneous psoriasis, before and after anti-IL-23 therapy.
Time frame: 7 years
Analysis of the frequencies of MAIT, iNKT, γδ TCR+, CD4+ et CD8+ T cells
Analysis of the frequencies of MAIT, iNKT, γδ TCR+, CD4+ et CD8+ T cells in the peripheral blood of patients with cutaneous psoriasis, before and after initiation of anti-IL-23 treatment to analyse the effect of anti-IL-23 therapy on the immune responses.
Time frame: 7 years
Definition of an immune response signature
immune response signature :gene expression, protein secretion or immune cell frequencies that correlates with therapeutic response to anti-IL-23 therapy in cutaneous psoriasis patients.
Time frame: 7 years
Identification of epigenetic modifications in cell populations in the skin and/or in circulating immune cells by anti-IL-23 therapy
analyzis of the effects of IL-23 inhibitors on gene expression in specific cell populations isolated from peripheral blood. Particular focis on CD4+ and CD8+ T cells, as well as monocytes.
Time frame: 7 years
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