Characterization of the Fungal Immunopeptidome Involved in the Immunopathological Mechanisms of Psoriasis (PSOFUNGI)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Psoriasis

Study type: Observational

Funder types: Other

Identifiers

NCT06610942

2024-A01701-46 (Other Identifier)

APHP240968

Details and patient eligibility

About

Psoriasis is a chronic immune-mediated skin disorder characterized by inflammatory cutaneous plaques and, occasionally, arthritis, affecting 60 million adults and children worldwide. Although a variety of treatments have been developed aimed to relieve the associated symptoms, there is yet no permanent cure for psoriasis. TH17 type immunity, via the production of IL-17A and other pro-inflammatory cytokines, are considered to play a central role in the pathogenesis of this disease. Moreover, experimental evidence obtained in animal models, points to human mycobiota as a trigger for the initiation and/or progression of psoriasis. Therefore, human studies are required to better characterize the major fungi implicated in the local and systemic inflammatory responses, as well as to determine the immunopeptidome that shapes the pathogenic T cell receptor repertoire.

We will explore the hypothesis that commensal fungi could participate in the chronic inflammatory immune response underlying the pathogenesis of human psoriasis via the recognition of cutaneous fungal antigens and/or via a gut-skin mycobiome cross-reactive mechanism

Full description

The overall aim of the project is :

i) to characterize the nature of human local and systemic inflammatory responses against commensal skin and gut fungal species in psoriatic patients (PsoP) and ii) to determine the fungal immunopeptidome that contributes to the shaping of the T cell receptor (TCR) repertoire of skin-infiltrating T cells. The project is divided into four major scientific objectives:

1. To determine the mycobiome profiles in healthy donors (HD) and PsoP.
2. To characterize the contribution of mycobiota to the local cutaneous CD4+ T cell response.
3. To assess systemic the CD4+ T cell-fungal cross-reactivity.
4. To establish the immunopeptidome of the major CD4+ T cell-reactive fungus enabling the development of an innovative immunotherapy.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Adults with psoriasis failing local treatment. Adults requiring reconstructive plastic surgery (resident skin immunology checks).

Adults living in the same household as a patient suffering from psoriasis (intestinal mycobiome checks).

Exclusion criteria

Minors Individuals under legal protection. Pregnant or breastfeeding women

Trial design

100 participants in 3 patient groups

Adult patients with psoriasis who have failed local treatment

"Healthy" controls (skin)

"Healthy" controls (stools)