Replicative Stress in Hair Follicle Stem Cells and Pathogeny of Hidradenitis Suppurativa (Fol-Hydra)

Hidradenitis Suppurativa is a recurrent chronic inflammatory follicular occlusive disease affecting hair follicles. HS is notoriously difficult and challenging to treat with a high morbidity impact and could be classified as an unmet medical need with no efficient therapeutic options.

Objective:

Investigators previously showed that Outer Root Sheath Cells (ORS) isolated from hair follicle of HS patients (HS-ORS) have a pro-inflammatory phenotype and secrete spontaneously IP-10 and RANTES. To identify the mechanisms involved in the pro-inflammatory phenotype of HS-ORS, investigators performed a transcriptomic analysis in healthy and HS patients. This revealed: (i) an IFN signature, (i) a dysregulation of genes involved in cell proliferation and differentiation, and (iii) an upregulation of DNA damage response and cell cycle G2/M checkpoint pathways in HS-ORS. These findings support the notion that, in HS patients, a perturbation of HF-SC homeostasis leading to an increased proliferation induces a replicative stress and an accumulation of cytoplasmic ssDNA, stimulating IFN synthesis through IFI16-STING pathway. Interestingly, replicative stress in ORS were present in some but not all patients with Hidradenitis Suppurativa. The goal of study is to determine replicative stress in ORS in a large cohort of HS patients.

Method Patients will be enrolled in the Mondor Dermatology department, during routine care. A dermatologist will check all inclusion and exclusion criteria with the technical support of a research technician of the Henri Mondor Clinical Investigation Center. Medical history, clinical data, comorbidities and concomitant therapies will be prospectively recorded in a dedicated case report form. Skin biopsies will be performed in perilesional zone rich in hair follicles. mRNA will be extracted from freshly isolated hair follicle cells and some slides will be prepared and stored at -80°C to perform immunohistochemistry analysis on freshly isolated hair follicle cells. PBMC and serum will be collected.

All these biological samples will allow us to quantify the replicative stress in HS-ORS of each patient, and to quantify several cytokine of interest : IFN de type 1, IL-17, IL-6, TNF-α, IL-10

This study will allow investigators to evaluate the rate of patients with replicative stress in hair follicle stem cells in Hidradenitis Suppurativa. The investigator will also determine whether HF-SC replication stress correlates with clinical characteristics and/or with clinical course and/or comorbidities.

Study Overview

• Status: Recruiting
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Other: Skin biopsy; Other: Blood sample

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claire HOTZ, MD; Phone Number: 33-1-49-81-37-96; Email: claire.hotz@aphp.fr
• Study Contact Backup: Name: Philippe Le Corvoisier, MD PhD; Phone Number: 33-1-49-81-37-96; Email: philippe.lecorvoisier@aphp.fr

Study Locations

• France
  • Val-de-marne
    • Créteil, Val-de-marne, France, 94010
      • Recruiting
      • Assistance Publique Hôpitaux de Paris - CHU HENRI MONDOR
      • Contact: Claire HOTZ, MD-PhD; Phone Number: 33-1-49-81-45-11; Email: claire.hotz@aphp.fr
      • Contact: Philippe Le Corvoisier, MD-pHD; Phone Number: 33-1-49-81-37-96; Email: philippe.lecorvoisier@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients referred to the consultation of dermatology of Henri Mondor Hospital
• Diagnosis of Hidradenitis Suppurativa
• Age> 18 y.o.
• Affiliation to a social security system

Exclusion Criteria:

• Patient under tutorship or curatorship
• Breastfeeding or pregnant women
• Refusal to sign the consent letter
• Patients benefiting from State Medical Aid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Physiopathologic exploration; A non randomised study with one arm, addind experimental acts to standard of care (skin biopsy and biological sample ) in order to explore Hidradenitis Suppurativa physiopathology	Other: Skin biopsy; A maximum of 2 superficial skin biopsies (epidermis/dermis), allowing 10 hair follicles to be obtained, at the edge of the affected area, in healthy territory (excluding the face and folds but not excluding the pubic region), at initiation visit.; Other: Blood sample; 42mL of blood (6 tubes of 7mL) sampled at initiation visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Replicative stress in hair follicle stem cells in Hidradenitis Suppurativa	Evaluation of the rate of patients with replicative stress in hair follicle stem cells in Hidradenitis Suppurativa	The primary outcome will be evaluated at baseline

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Estimated): June 13, 2029
• Study Completion (Estimated): December 13, 2029

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: inflammation; cytokine; Hidradenitis Suppurativa; replicative stress
• Additional Relevant MeSH Terms: Infections; Skin Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Sweat Gland Diseases; Skin Diseases, Bacterial; Skin Diseases, Infectious; Suppuration; Hidradenitis Suppurativa; Hidradenitis
• Other Study ID Numbers: APHP211351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No