Exploration of the Cellular and Molecular Mechanisms in Patients Receiving Biotherapies Targeting the IL-23/IL-17 Axis in Cutaneous Psoriasis

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.

Inclusion criteria

All patients:

• Adults (>18 years)
• Presenting with cutaneous psoriasis
• Patients have signed an informed consent
• Beneficiary of the health insurance, except for the AME Only for patients of Group 1
• Patients require systemic treatment for psoriasis
• Patients are naïve to biological therapies

Only for patients of Group 2:

• Patients requiring treatment with anti-IL-23 biologics (guselkumab, risankizumab, tildrakizumab) upon referent physician's decision.
• Patients are naïve to biological therapies or have received only one biologic, with a "wash-out" period of at least 4 months

Non inclusion Criteria:

For all :

• Patient is minor
• Patient is pregnant or breastfeeding
• Patient is immunocompromised
• Patient is under legal protection, curatorship, guardianship
• Patient refuses consent
• Patient is unable to comply with study requirements for geographic, social or psychiatric reason.
• Beneficiary of the AME Only for patients of Group 1
• Patient has received biologics Only for patients of Group 2
• Patient has a contraindication to the chosen biotherapy
• Patient has received biologics within the last 4 months
• Patient has been treated with 2 or more biologics
• Patient has already received an anti-IL-23 biologic