Deciphering IL-17-dependant Inflammatory Response in Bullous Pemphigoid

CHU de Reims140 enrolled

Overview

Bullous pemphigoid (BP) is the most frequent autoimmune skin disease and mainly affects elderly individuals. BP classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense itches. However, BP is characterized by a large spectrum of clinical presentations allowing to distinguish between typical (with blisters) and atypical forms (non bullous, mucosal damage). High potency topical steroids and systemic steroids are the current first line intention treatments. While very efficient, these therapies are non-targeted and cause numerous side-effects, especially in these elderly patients that are the most affected. Furthermore, around 30% of BP patients will relapse during the first year of treatment when corticotherapy is decreased or stopped. The investigators and others have highlighted the presence of Il-17 family belonging-inflammatory cytokines in BP patients. Their functions in the amplification of the inflammatory response and in the mechanisms of relapse have to be precisely determined in order to develop innovative therapeutic approaches and to move forwards precision medicine.

This is a pathophysiological study with prospective and monocentric inclusion. 90 patients with bullous phemphigoid will be recruited from the department of dermatology at the Reims University Hospital. The main objectives of this study are to identify the cellular and molecular actors of the IL-17B/IL-17RB axis at diagnosis in patients with bullous pemphigoid and to determine their functions in the pathophysiological mechanisms associated with BP at systemic and in situ levels. The secondary aims of this research are: 1. To confirm IL-17B concentrations in sera at diagnosis as predictive biomarker of BP outcome under local corticotherapy 2. To study the expression kinetics of IL-17B and its receptor IL-17RB in BP patients under treatment 3. To study the implication of IL-17B/IL-17RB axis in BP relapse 4. To establish inflammatory cell composition profile in skin and blood issued from clinical variants of BP as well as from BP patients during the first year of treatment.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Interventions

Blood samplingBIOLOGICAL

Venous blood sampling will be carried out for each patient included in the study.

Liquid bubble samplingBIOLOGICAL

Liquid bubble sampling will be carried out for each patients with Bullous Pemphigoid included in the study.

Cutaneous biopsyPROCEDURE

At least the first cutaneous biopsy will be carried out for each patients with Bullous Pemphigoid included in the study.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * patients with Bullous Pemphigoid (BP) using the following criteria: clinical features typical of BP with presence of at least three out of four well-established criteria by Vaillant et al.47; subepidermal blister on skin biopsy; and deposits of IgG and/or C3 in a linear pattern along the epidermal basement membrane zone by direct IF. * patient agreed to participate to the study * patient affiliated to the French Healthcare System Exclusion Criteria: * patient that does not have the ability to give its written informed consent before inclusion in the study * patient with a pemphigoid gestationis * patient with a relapse of Bullous Pemphigoid * patient with Bullous Pemphigoid that already received local superpotent corticotherapy during the last 14 days before inclusion or systemic corticoid treatment during the last 28 days before inclusion * anemic patient (hemoglobin \< 10 g/dL)

Outcomes

Primary Outcomes

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 1

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 30

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 60

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 90

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 150

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 270

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood

Identification of IL-17RB-expressing cells and IL-17B-producing cells in blood from whole blood of patients with BP or control subjects using flow cytometry

Time frame: Day 365

Identification of IL-17RB-expressing cells at the lesional site

Identification of IL-17RB-expressing cells at the lesional site from BP skin biopsy specimen harvested using histocytometry

Time frame: Day 1

Identification of IL-17RB-expressing cells at the lesional site

Identification of IL-17RB-expressing cells at the lesional site from BP skin biopsy specimen harvested using histocytometry

Time frame: Day 60