Analysis of Sexual Bias in Type 2 Innate Lymphoid Cells (ILC2) in Asthmatic Patients (IL-C2)

Analysis of Sexual Bias in Type 2 Innate Lymphoid Cells (ILC2) in Asthmatic Patients: Role of Androgens

Asthma is more common in females than in males but the difference has not been explained yet. Group 2 innate lymphoid cells (ILC2) have recently emerged as critical players in the initiation of allergic responses but their implications in the difference between males and females in terms of asthma prevalence has not been fully studied. The aim of this project is to compare the proportion of ILC2 in blood between males and females with asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Blood sample collection (one tube); Biological: Blood sample collection (five tubes)

Detailed Description

Asthma is more common in males until puberty but becomes more prevalent and more severe in females after puberty suggesting a protective action of male sex hormones. ILC2 have recently emerged as critical players in the initiation of allergic responses. The present team established that androgens, signaling through the nuclear receptor 3 C4 (NR3C4) androgen receptor (AR), negatively control ILC2 at steady state and during lung inflammation. Relevant to this application, females with asthma have more circulating ILC2 than males. The present hypothesis is that harnessing AR signaling in ILC2 may provide a new therapeutic approach to down regulate tissue resident ILC2. This project will analyze the sex bias in circulating ILC2 in female and male patients with moderate to severe asthma. In females with asthma, the team will purify circulating ILC2 from peripheral blood mononuclear cells (PBMC) and expand them in vitro using cytokines and stromal cells in the presence of AR antagonist or agonist ligands. Bulk ILC2 cultures at day 7 will used to measure the expression profile of various gene, including AR.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

• Study Contact: Name: Laurent Guilleminault, MD PhD; Phone Number: 0033 567771850; Email: guilleminault.l@chu-toulouse.fr
• Study Contact Backup: Name: Julie Milia; Phone Number: 0033 567771624; Email: milia.j@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France, 31059
    • Larrey Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Asthma patients

Description

Inclusion Criteria:

• Asthma according to the criteria described by Global Initiative for Asthma (GINA) guidelines
• Severe asthma according to the criteria described by the American Thoracic Society (ATS) / European Respiratory Society (ERS) guidelines (for the recruitment of severe patients)
• Mild to moderate asthma based on low or medium dose of inhaled steroids according to GINA guidelines

Exclusion Criteria:

• Asthma exacerbations defined as oral corticosteroids related to worsening respiratory symptoms within the past 4 weeks
• Pregnant women
• Breastfeeding women
• Autoimmune diseases
• Androgen medication
• Early menopause defined as the absence of menstruation for at least 1 year
• Body mass index ≥ 30 kg/m²
• Weight <40 kg
• Oral corticotherapy for more than 3 months
• Prediction of blood volume collected (care + research)> 80 ml or> 150 ml over a period of 30 days if blood collection within the past 30 days
• known anemia with hemoglobin <10 g/dl

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mild to moderate asthma; low or medium dose of inhaled steroids according to GINA guidelines	Biological: Blood sample collection (one tube); Collection of one tube of 7.5 ml blood in addition to a blood sample made in clinical practice
Severe asthma; criteria described by the ATS / ERS guidelines (for the recruitment of severe patients)	Biological: Blood sample collection (five tubes); Collection of five tubes of 7.5 ml blood in addition to a blood sample made in clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of circulating ILC2 between gender with asthma.	Estimation of the proportion of circulating ILC2 between males and females with asthma.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of circulating ILC2 according to asthma severity.	Estimation of the proportion of circulating ILC2 between mild to moderate asthma patients and severe asthma patients.	Day 1
Comparison of the effect of (androgenic receptor) AR ligands in a culture of ILC2.	ILC2 purified form PBMC of asthmatic females will be expanded in vitro in the presence of AR antagonist or agonist ligands. Bulk ILC2 cultures at day 7 will used to measure the expression profile of various gene, including AR.	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Laurent GUILLEMINAULT, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: allergy; type 2 innate lymphoid cells
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: RC31/20/0007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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