The Role of Host-microbiota Interplay in Hidradenitis Suppurativa Pathogenesis

Hidradenitis Suppurativa (HS) is a chronic disabling inflammatory skin disorder associated with the development of painful and purulent lesions of the folds (armpits, inguinal folds, sub-mammary glands). HS most often develops in adolescence or young adulthood and is characterized by inflammation of the pilo-sebaceous system, of progressive severity (folliculitis, nodule, abscess, fistula). The pathogenesis of HS is still poorly understood: the fact that patients respond to combinations of antibiotics and/or immunosuppressive treatments suggests that the disease could be due to a dysregulated immune response against microbial skin flora. Unconventional lymphocytes (UL), classically considered being at the interface of innate and adaptive immunity, play an important role in immune protection against microbial flora. But UL dysfunction has also been reported in many autoimmune diseases involving various tissues (joints, digestive tract, skin). The uncontrolled and chronic activation of these UL by skin microbiota could therefore play a role in the pathogenesis of HS.

The aim of this exploratory study is to analyze the interplay between microbiota and the innate and adaptative immune response in the pathogenesis of HS. To better understand this host-microbiota interplay, we will assess the number, frequency and functional phenotypes of the different lymphocyte subsets in HS patients, with a special focus regarding the UL. In the same time, we will assess the diversity and nature of skin microbiota of the same patients. Finally, we will explore the relation between the immune response and the skin microbiota in HS, using correlation analysis (Spearman coefficient).

In this study, HS patients will be their own control for leucocyte phenotyping, cytokine analysis and T Cells Receptor (TCR) sequencing (skin biopsies) and for skin microbiota analysis. Paired (age/sex) healthy volunteers will be controls for gut microbiota analysis and for immunophenotyping of circulating leukocytes (Peripheral Blood Mononuclear Cells (PBMC) analysis).

Eligibility Criteria:
Inclusion Criteria:

* Subject able to read, understand and give documented informed consent
* Subject willing and able to comply with the protocol requirements for the duration of the study
* Subject with health insurance coverage according to local regulations
* For woman with childbearing potential, negative pregnancy test at the inclusion visit Specific criteria for HS patients
* Subject diagnosed with HS for at least 6 months
* Subject diagnosed with moderate-to-severe HS defined by HS PGA≥3
* Subject presenting an HS with inflammatory phenotype defined by the presence of folliculitis, nodules and/or abcesses
* Subject suffering from at least 4 flares/year and presenting 5 active inflammatory lesions (nodules and/or abcesses)

Exclusion Criteria:

* Pregnancy or breast-feeding women
* Subject treated by allergen immunotherapy within 4 weeks before inclusion
* Subject treated by Non-Steroidal Anti-Inflammatory Drugs (NSAID), antibiotics or proton-pump inhibitors within 4 weeks before inclusion
* Subject treated by live (attenuated) vaccine within 4 weeks before inclusion
* Subject treated by anti-viral treatment within 4 weeks before inclusion
* Subject treated by anti-diarrhea treatment including, but not limited to Loperamide
* Subject treated by immunosuppressive/immunomodulatory substances including oral corticosteroid or biological agents within 4 weeks before inclusion
* Subject presenting spondylo-arthritis or Inflammatory Bowel Disease (IBD)
* Subject with a Body Mass Index (BMI)\<18.5 or BMI\>35
* Subject consuming probiotics or using a specific diet (e.g. gluten free, vegetarian, vegan, intermittent fasting)
* Subject with any additional condition that, in the opinion of the investigator, may interfere with the assessment or put the subject at risk
* Linguistic or mentally incapacity to sign the consent form
* Subject protect by the law (adult under guardianship, or hospitalized in a public or private institution for a reason other than study, or incarcerated)
* Subject in an exclusion period from a previous study or who is participating in another clinical trial using a drug Specific criteria for HS patients
* Subject currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of HS
* History of allergic reaction to local anesthetic product
* History of wound healing disorders (e.g. hypertrophic scars, keloids)
* History of extensive armpit surgery
* Subject with known active infection to Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV)
* Subject treated for their HS by systemic therapy, investigational or commercial, approved or off label)
* Subject treated for their HS by immunosuppressants or intralesional corticosteroids within 4 weeks before the inclusion
* Subject treated for their HS by topical antibiotics within 4 weeks before the inclusion
* Subject previously treated with monoclonal antibodies