Sensory Nociceptive Nerve Fibers, Key Regulator of Immune Response Type 2 in Atopic Dermatitis

NCT04193670 | Completed DMC

• 1 other identifier: RC31/19/0118
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The skin is innervated by a network of nociceptive sensory neurons (nociceptors) whose primary function is the transmission of pain and pruritus signals to the central nervous system. Their role in atopic dermatitis (AD), characterized by an exacerbated type 2 immune response, is only partially understood. Nevertheless, large amounts of neuropeptides, including substance P (SP), are found in the serum of patients, their level being correlated with the clinical severity of AD. Mast cells (MC) are part of the cells of the immune system residing in the skin. MCs have neuro-receptors of the Mas-related G protein-coupled receptors family (MRGPR) and in particular MRGPRX2 (the receptor for cationic molecules \[including SP\] for MCs) through which they could communicate in a privileged way. with the nociceptors. Preliminary data obtained in mice show that its mouse orthologue "MrgprB2" is absolutely necessary for the development of type 2 immunity and the pathological characteristics of a preclinical "DA-like" model (manuscript in preparation). The investigators therefore hypothesize that the activation of MCs expressing MRGPRX2 by nociceptors producing SP plays a key role in the development of type 2 inflammation in AD in humans.

Conditions

Atopic Dermatitis

Keywords

nociceptors- immune response; atopic prurigo

Outcome Measures

Primary Outcomes (1)

• Characterization of neuronal interactions by two-photon microscopy

  quantification by two-photon microscopy of the density of nerve fibers producing SP, the density of MRGPRX2 + MCs, the spatial proximity between nerve fibers and MC and quantification of the degranulated appearance of MC in the lesional skin of patients with DA classical form and DA atopic prurigo type in comparison to the skin of control subjects.

  13 months

Secondary Outcomes (2)

• Marker analysis by ELISA assay

  13 months

• Cellular analysis

  13 months

Study Arms (2)

Atopic dermatitis classical form

EXPERIMENTAL

15 patients

Other: Clinical examination; Procedure: Biopsies; Other: Blood test

Atopic dermatitis with atopic prurigo type

EXPERIMENTAL

10 patients

Other: Clinical examination; Procedure: Biopsies; Other: Blood test

Interventions

Clinical examination OTHER

This is a classic dermatological clinical examination during a classic consultation

Atopic dermatitis classical form; Atopic dermatitis with atopic prurigo type

Biopsies PROCEDURE

2 skin biopsies on a lesion area selected according to the inclusion criteria (2 punchs of 4 mm) for each experimental group. The first half of whole cutaneous biopsies (n = 25) will be studied using biphotonic microscopy. This will be performed on whole biopsies in 3-D according to the protocol developed in the laboratory. The second half of whole skin biopsies (n = 25) will be studied using the technique of single-cell RNA seq. The skin controls skin-free subjects will be obtained from skin reduction surgery (abdominoplasty) to subjects who have agreed to the use of their skin sample.

Atopic dermatitis classical form; Atopic dermatitis with atopic prurigo type

Blood test OTHER

A blood test on a tube (2 tubes of 10 mL).An assay of specific IgE and the serum level of IL-4, IL-13 and IL-5 will be carried out by ELISA (Enzyme Linked ImmunoSorbent Assay) from the blood samples.The blood samples will be obtained through the French blood establishment from different donors who have given their consent.

Atopic dermatitis classical form; Atopic dermatitis with atopic prurigo type

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Criteria for the study population:
• Subject affiliated with a social security scheme or beneficiary of such a scheme;
• subject who has given written consent to participate in the study;
• Subject accepting a blood test to check for the absence of infectious diseases (HIV serologies, Hepatitis B, Hepatitis C) in the event of a blood exposure accident;
• Subject accepting biopsies
• Criteria related to the pathology studied:
• Subject with atopic dermatitis according to UK Working Party criteria or Williams criteria with an IGA score ≥ 3 (group 1)
• Subject with atopic dermatitis according to UK Working party criteria or Williams criteria in the form of an atopic prurigo diagnosed by the dermatologist (group 2)
• Criteria relating to control subjects: Subjects who had abdominoplasty and agreed to use their skin sample as part of Genoskin (Ministerial Approval # AC-2017-2897) (Group 3).
• Criteria for treatment:

You may not qualify if:

• Criteria for the study population:
• Solar exposure of biopsied areas planned during the study;
• Criteria related to the pathology studied:
• Chronic inflammatory dermatosis other than classical AD or atopic prurigo at sites to be harvested;
• Subject with a known history of allergy or intolerance to local anesthetics, local antiseptics to latex or plaster;
• Subject already having abnormalities of healing
• Subject with a recognized addiction to alcoholism or drug addiction;
• Subject having an inherited or acquired disease of hemostasis;
• Subject having a severe or acute chronic condition deemed by the investigator to be inconsistent with the trial;
• Subject with immunodeficiency clinically incompatible with the study.
• Criteria for treatment:
• Any topical or systemic treatment of AD (including phototherapy) in progress
• ongoing systemic treatment that may interfere with the healing process;
• Subject having undergone a physical treatment (radiotherapy, ...) on the area to be biopsied, during the last 6 months.
• History of treatment or concomitant treatment that may interfere with the completion of the study according to the opinion of the investigator.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

CHU de TOULOUSE

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

Restraint, Physical; Biopsy; Hematologic Tests

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Marie TAUBER

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 10, 2019
• Study Start: May 7, 2019
• Primary Completion: February 3, 2022
• Study Completion: December 31, 2022
• Last Updated: July 24, 2023

Record last verified: 2023-07

Locations

FR (1)