Hidradenitis suppurativa (HS), also known as Verneuil's disease, is a chronic inflammatory dermatosis of the hair follicule located mainly in the skin folds (axillae, inguinal, submammary, etc.). Currently, treatments are mainly limited to the use of broad-spectrum antibiotics in order to control outbreaks of hidradenitis suppurativa. Surgical treatment is the only curative treatment, but requires disfiguring removals with major scarring consequences. Pathophysiologically, HS appears to be a primary abnormality of the pilosebaceous-apocrine unit, causing follicular occlusion, followed by the development of perifollicular cysts with commensal bacterial overgrowth, and finally rupture into the dermis causing an exaggerated inflammatory response. At present, few studies have examined the role of the regulatory immune system and its involvement in this disease. We are also interested in analyzing the impact of new therapeutic strategies on hidradenitis suppurativa, and more particularly the impact of photodynamic therapy (PDT) which is a technique that has been used for a long time in dermatology, notably for the treatment of precancerous and cancerous lesions. This technique has shown interesting results on inflammatory dermatoses such as acne. This research consists in studying the immunomodulation of the immune response in HS and in evaluating a new therapeutic strategy based on PDT alone or in combination with antimicrobial peptides (PAMs).
Hidradenitis suppurativa (HS), also known as Verneuil's disease, is a chronic inflammatory dermatosis of the hair follicule located mainly in the skin folds (axillae, inguinal, submammary, etc.). The disease is characterized by pain, inflammatory nodules, abscesses, fistulas and hypertrophic " rope " scars that considerably alter the quality of life of patients. Currently, the treatment is mainly limited to the use of broad-spectrum antibiotics in order to control the outbreaks of HS. This medical treatment is currently controversial because of the risk of inducing bacterial resistance. Surgical treatment is the only curative treatment, but requires disfiguring removals with major scarring consequences. Pathophysiologically, HS appears to be a primary abnormality of the pilosebaceous-apocrine unit, which causes follicular occlusion, followed by the development of perifollicular cysts with commensal bacterial proliferation, and finally rupture into the dermis causing an exaggerated inflammatory response. At present, few studies have examined the role of the regulatory immune system and its involvement in this disease. In the context of HS, it has recently been shown from patient samples that there is an abnormality concerning the stem cells present in the follicular bulb. It can be asked whether the abnormalities observed in hair follicle stem cells of HS patients could be the source of pro-inflammatory exosomes playing a role in HS flares. The impact of new therapeutic strategies on hidradenitis suppurativa, and more particularly the impact of photodynamic therapy (PDT) which is a technique used for a long time in dermatology, notably for the treatment of precancerous and cancerous lesions will be also evaluated. This technique has shown interesting results on inflammatory dermatoses such as acne with an " antibiotic " effect. Thus, this research consists in studying the immunomodulation of the immune response in HS and in evaluating a new therapeutic strategy based on PDT alone or in combination with antimicrobial peptides (PAMs). This is a prospective observational multicenter study of type 3. This study is composed of two steps : first an in vitro part, secondly an ex vivo part allowing to validate the results obtained in vitro on human samples.
Study Type
OBSERVATIONAL
Enrollment
20
For patients, it will be performed: * a collection of blood samples (3 tubes of 5 mL) according to the usual medical management, in order to search for cardiovascular comorbidities associated with HS, * A collection of 3 EDTA tubes and 2 additional dry tubes of 5 mL each according to the needs of the study.
For patients, it will be performed: \- 6 tissue samples from the total excision specimen: two samples from the acute inflammatory zone (nodule, abscess, fistula) of 1 cm3; two samples from the chronic lesion zone (scar) of 1 cm3 and two samples from the peri-lesion zone (in the margin) of 1 cm3 on fresh tissue.
For the controls, 6 fresh skin samples of 1 cm3 each will be taken from the abdominoplasty operation: * four in the center, * two in the margin
Hôpital Saint Vincent-de-Paul, Service de Dermatologie-Vénéréologie
Lille, France
Hôpital Saint Philibert - Service de Chirurgie Viscérale
Lomme, France
Prevalence of different types of immune cell populations
Prevalence of cell populations will be determined by cytometry
Time frame: Day 0
Activation of lymphocytes
The activation state of circulating lymphocytes will be analyzed by flow cytometry using antibodies coupled to fluorochromes specifically targeting the following membrane markers: CD4, CD30, CD69, Anti-HLADR, CD152, CD197, CD25, CD8.
Time frame: Day 0
Prevalence of innate lymphoid cells
The prevalence of innate lymphoid cells will be determines by cytometry
Time frame: Day 0
Gene expression analysis
A microarray assay will be performed in order to determine the expression of genes of interest.
Time frame: Day 0
Secretome analysis
The pg/mL concentrations of different cytokines in the serum of HS patients versus healthy controls will be determined using ELISA (Luminex™) in order to be able to determine the differences in activation of immune pathways : Th1/Th2, Th9/Th17/Th22/Treg, inflammatory cytokines, Immunosuppressive cytokine.
Time frame: Day 0
Size of exosomes
The size of exosomes will be measured by the Tunable resistive Pulse sensing method
Time frame: Day 0
Concentration of exosomes
The concentration of exosomes will be measured by the Tunable resistive Pulse sensing method
Time frame: Day 0
Quantification of antimicrobial peptides
Several antimicrobial peptides such as elafin/SHALP, dermcidin, S100A7/psoriasin, S100A8/calgranulin A, S100A9/calgranulin B, LL-37 (cathelicidin), h-βd1, h-βd2, h-βd3, h-βd4, ribonuclease 7, SLPI/ALP from HS patient serum versus blood baqs (control) as well as in supernatants of HS lesion tissue versus abdominoplasty tissue (control) cultured in microslices will be quantified by ELISA
Time frame: Day 0
Quantification of wound healing
Wound healing capacity We will evaluate the ability to restore wound healing in in vitro HS models (HaCaT NCSTN-/-line) versus the healthy model (HaCaT wild type) by performing wound healing and migration assays (IBIDI) with and without the addition of exogenous PAMs lacking in HS.
Time frame: Day 0
Efficacity of the Photodynamic Therapy (PDT)
Time frame: Day 0
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