Deciphering IL-17-dependant Inflammatory Response in Bullous Pemphigoid (BP-IL17RB)

Identification and Functional Characterization of the Cellular and Molecular Actors of the IL-17B/IL-17RB Axis in Bullous Pemphigoid

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.

Study Overview

• Status: Recruiting
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Biological: Blood sampling; Biological: Liquid bubble sampling; Procedure: Cutaneous biopsy

Detailed Description

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
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manuelle VIGUIER, Pr.; Phone Number: 03.10.73.66.76; Email: mviguier@chu-reims.fr
• Study Contact Backup: Name: Sébastien LE JAN, Dr.; Phone Number: 03.26.91.35.24; Email: sebastien.le-jan@univ-reims.fr

Study Locations

• France
  • Reims, France, 51092
    • Recruiting
    • Chu Reims
    • Contact: Damien JOLLY, Pr.; Phone Number: 33 326788472; Email: djolly@chu-reims.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control subjects	Biological: Blood sampling; Venous blood sampling will be carried out for each patient included in the study.
Experimental: Patients with Bullous Pemphigoid	Biological: Blood sampling; Venous blood sampling will be carried out for each patient included in the study.; Biological: Liquid bubble sampling; Liquid bubble sampling will be carried out for each patients with Bullous Pemphigoid included in the study.; Procedure: Cutaneous biopsy; At least the first cutaneous biopsy will be carried out for each patients with Bullous Pemphigoid included in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	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	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	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	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	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 1
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 30
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 60
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 90
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 150
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 270
Measurement of IL-17B concentrations in sera	Measurement of IL-17B concentrations in sera of patients with BP using ELISA technique	Day 365

Collaborators and Investigators

• Sponsor: CHU de Reims

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): January 10, 2025
• Study Completion (Estimated): January 10, 2026

Study Registration Dates

• First Submitted: June 14, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: inflammatory response; Bullous pemphigoid; IL-17 family
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous
• Other Study ID Numbers: PO21096

Drug and device information, study documents

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