MAIT Cells in Hidradenitis Suppurativa

Overview

Hidradenitis Suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by painful, purulent lesions primarily in skin folds. Its pathogenesis remains poorly understood. The clinical benefit observed with both antibiotics and immunosuppressive therapies suggests HS may involve an abnormal immune response to skin microbiota. Mucosal-associated invariant T (MAIT) cells are immune cells that bridge innate and adaptive immunity and are known to regulate microbial flora. Dysfunctional MAIT cells have been implicated in autoimmune diseases such as type 1 diabetes, inflammatory bowel diseases, and psoriasis. Preliminary data from the VERIMMUNE study (NCT05735925) indicate that HS patients show a depletion of circulating MAIT cells and increased infiltration of CD8+ MAIT cells in lesions, associated with reduced activation and greater disease severity. These findings support the hypothesis that MAIT cell dysfunction plays a central role in HS and may serve as a biomarker for treatment response. This exploratory study aims to (Primary) characterize the phenotype and frequency of MAIT cell subsets in the skin and blood of HS patients compared to controls with other inflammatory skin diseases (psoriasis and back-acne); and to determine whether MAIT cell phenotype before treatment predicts clinical response to biologic agents. The study will recruit adults (18-65 years) with moderate-to-severe HS and matched controls with plaque psoriasis, or back-acne, or impetigo. All HS participants must be biologic-naïve at baseline and will be treated per national guidelines (adalimumab, secukinumab, or bimekizumab). No therapeutic intervention is imposed; patients are followed according to usual care. Skin and blood samples will be collected before and after treatment to assess immune profiles. To minimize bias HS patients will be age/sex-matched with controls; only patients with active, inflammatory HS lesions will be included; controls were selected to represent related yet distinct pathologies: back-acne (follicular but distinct mechanism), psoriasis (different lesion type, shared type-17 inflammation) and impetigo (skin bacterial infection). The Immunophenotyping strategy will use high-dimensional flow cytometry (Cytek® Aurora); researchers will analyze immune cell subsets (e.g., B cells, γδ T cells, NK cells, ILCs, MAIT, NK-T) in skin and blood. Specific markers for activation (CD69, PD-1, ICOS), differentiation (CCR7, CD45RA), proliferation (Ki-67), cytokine receptors, and chemokines will be assessed. The primary endpoint will be the frequency of MAIT cells in lesional vs. non-lesional skin and blood compared to controls before and after 12 weeks of biologic agent. The secondary endpoints will be changes in MAIT cell phenotype after 12 weeks of treatment, correlation with clinical improvement (defined by IHS4-55 response: ≥55% reduction in IHS4 score) and MAIT cell functions (assessed in vitro before and after treatment, anti-bacterial activity, capacity to proliferate and to be activated). This is a prospective, monocentric, exploratory study with intra-individual comparison and external active controls. The study falls under category 2 (interventional research with minimal risks). Clinical data, biopsy samples, and immune profiles will be collected before and after biologic therapy in moderate-to-severe HS patients (IHS4 ≥4), biologic-naïve, eligible for biologic agents treatment, with no antibiotics or immunosuppressive drugs in the prior month. The controls will be adults with psoriasis or back-acne or impetigo (no follow-up for control patients). This study has no direct therapeutic benefit for participants. However, it offers detailed clinical follow-up and may significantly improve understanding of HS pathogenesis. Known procedural risks (local anesthesia, biopsy, venipuncture) are minimal and mitigated through standard precautions and inclusion criteria. Expected benefits and impact : clarify the role of MAIT cells in HS pathophysiology; identify novel immune biomarkers predictive of biologic therapy response; support future therapeutic stratification and personalized treatment approaches in HS.