Innate Immunity in Eosinophilic Esophagitis (CLOE)

Innate Lymphoid Cells in Eosinophilic Esophagitis (French Title : Cellules Lymphoïdes innées Dans l'Oesophagite à Eosinophiles)

The main aim of this study is to assess the expression of innate lymphoid cells in the esophageal mucosa of children with eosinophilic esophagitis (EoE) and in control subjects

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Other: Endoscopy

Detailed Description

Children (aged 1 to 18 years) presenting with symptoms suggestive of EoE and requiring an upper gastrointestinal endoscopy with biopsies of the esophageal mucosa in order to confirm or exclude the diagnosis of EoE will be included.

Children paired for age in whom an endoscopy performed to explore symptoms of EoE revealed another condition (peptic oesophagitis, achalasia), or children paired for age in whom an endoscopy with biopsies has been performed to explore chronic abdominal or epigastric pain or suspected chronic inflammatory bowel disease, will be include as control subjects.

The endoscopy will be performed under general anaesthesia using a flexible endoscope with an external diameter of between 4.9 and 9.2 mm, depending on the size of the child. In line with the guidelines, eight biopsies will be collected from the proximal, median and distal oesophagus for the routine analysis of esophageal remodelling and inflammation. Three of these biopsies will be used in the context of this study to analyse innate immune cells using flow cytometry and to determine the profile of cytokine expression. Two biopsies will be placed in sterile, 0.5 ml Nunc tubes containing a storage buffer (MACS® Tissue Storage Solution) and then stored in ice until the extraction of cells for cytometric analysis. The third specimen will be placed in a sterile tube and frozen immediately in liquid nitrogen for analyses of the esophageal microbiome.

ILC1, 2 and 3 and their sub-types will be identified by means of structural criteria (size and granularity) and differential membrane and intracellular labelling using the specific markers shown below. All acquisitions and analyses will be achieved using a 13-colour NovoCyte cytometer (AACEA) and its associated software (NovoAxpressTM), which are available in the laboratory.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Necker-Enfants Malades Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children presenting with symptoms suggestive of EoE and requiring an upper gastrointestinal endoscopy with biopsies of the esophageal mucosa

Description

Inclusion Criteria:

• children 1-18 years
• presenting with symptoms suggestive of EoE
• requiring an upper gastrointestinal endoscopy with biopsies of the esophageal mucosa in order to confirm or exclude the diagnosis
• Children paired for age in whom an endoscopy performed to explore symptoms of EoE revealed another condition (peptic oesophagitis, achalasia), or children paired for age in whom an endoscopy with biopsies has been performed to explore chronic abdominal or epigastric pain or suspected chronic inflammatory bowel disease, will be include as control subjects

Exclusion Criteria:

• immune deficiency
• auto immune diseases

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
case : eosinophilic esophagitis; Children with symptoms suggestive of EoE and requiring an upper gastrointestinal endoscopy with biopsies of the esophageal mucosa	Other: Endoscopy; The endoscopy will be performed under general anaesthesia using a flexible endoscope with an external diameter of between 4.9 and 9.2 mm, depending on the size of the child. In line with the guidelines, eight biopsies will be collected from the proximal, median and distal oesophagus for the routine analysis of esophageal remodelling and inflammation. Three of these biopsies will be used in the context of this study to analyse innate immune cells using flow cytometry and to determine the profile of cytokine expression. Two biopsies will be placed in sterile, 0.5 ml Nunc tubes containing a storage buffer (MACS® Tissue Storage Solution) and then stored in ice until the extraction of cells for cytometric analysis . The third specimen will be placed in a sterile tube and frozen immediately in liquid nitrogen for analyses of the esophageal microbiome.
control; Children in whom an endoscopy performed to explore symptoms of EoE revealed another condition (peptic oesophagitis, achalasia), or children in whom an endoscopy with biopsies has been performed to explore chronic abdominal or epigastric pain or suspected chronic inflammatory bowel disease	Other: Endoscopy; The endoscopy will be performed under general anaesthesia using a flexible endoscope with an external diameter of between 4.9 and 9.2 mm, depending on the size of the child. In line with the guidelines, eight biopsies will be collected from the proximal, median and distal oesophagus for the routine analysis of esophageal remodelling and inflammation. Three of these biopsies will be used in the context of this study to analyse innate immune cells using flow cytometry and to determine the profile of cytokine expression. Two biopsies will be placed in sterile, 0.5 ml Nunc tubes containing a storage buffer (MACS® Tissue Storage Solution) and then stored in ice until the extraction of cells for cytometric analysis . The third specimen will be placed in a sterile tube and frozen immediately in liquid nitrogen for analyses of the esophageal microbiome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The numbers of innate immune cells	The counts of innate immune cells will be compared between EoE patients and controls	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota	Analyses of the composition of the esophageal microbiome will be performed using 16S rDNA sequencing after the extraction of DNA according to published protocols and/or using commercial kits (QlAamp DNA stool Mini Kit; QIAGEN). The pyrosequencing of 16S DNA, the identification of groups and phyla and initial biostatistical analyses will be carried out by specialised platforms.	1 year
Metabolomics	Metabolomic analyses will be performed on plasma and red blood cell extracts using a device such as an Orbitrap-Exactive equipped with an electrospray source. The data will be analysed using data processing tools available in the laboratory (software systems for signal detection and automatic alignment, annotation and statistical analysis)	1 year

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Guillaume LEZMI, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2018
• Primary Completion (Actual): October 28, 2019
• Study Completion (Actual): October 28, 2019

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: children; innate immunity; eosinophilic esophagitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis
• Other Study ID Numbers: NI17020JHLJ

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