Autophagy in Paediatric Crohn's Disease

Study Overview
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Brief Summary
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Crohn's disease is a multifactorial complex disease resulting in a between microbiota and immune system. Indeed, GWAS (Genome-Wide Association Studies) association study pinpointed polymorphisms as genes susceptibility on more than 200 loci. Among them genes coding for proteins involved in autophagy machinery (i.e: ATG16L1, IRGM et NDP52). Autophagy is a ubiquitous intracellular mechanism mandatory for protein and microorganism recycling. So far, the role of autophagy in gut inflammation and intestinal homeostasis in Crohn's disease patients is partially understand. Then, investigators plan to evaluate, on native cells, the autophagic flux in pediatric patients suffering of a Crohn's disease compare to controls.

Official Title
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Autophagic Activity Characterization in Pediatric Crohn's Disease

Conditions
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Crohn Disease, Pediatric Crohns Disease

Intervention / Treatment
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* Other: Blood samples
* Other: Biopsies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Crohn's Disease group : Age between 6 and 17 inclusive Patients with a weight > 25 kg at the time of inclusion Patients with Crohn's disease requiring ileocolonoscopy (diagnosis or follow-up) Mild to severe Crohn's disease consistent with PCDAI disease activity score Patients on nutritional therapy (Modulen/Modulife), corticosteroids, salicylic derivatives, immunosuppressants, biotherapies (anti-TNF, vedolizumab and ustekinumab) or without treatment Consent form signed by the patient or the holder(s) of parental authority. Affiliation to a social security scheme or beneficiaries of a similar scheme. For Control group: Between 6 and 17 years old included Presenting a weight > 25 kg at the time of inclusion Without a diagnosis of Crohn's disease Requiring evaluation by ileoendoscopy Consent form signed by the patient or the holder(s) of parental authority. Affiliation to a social security scheme or beneficiaries of a similar scheme. Exclusion Criteria: Refusal to participate in the protocol Intercurrent infection Ongoing antibiotic treatment Patient involved in another interventional study protocol including an exclusion period still in progress at pre-inclusion Pregnant, parturient or breastfeeding women (on questioning) Persons deprived of their liberty by a judicial or administrative decision Persons subject to psychiatric care Persons admitted to a health or social establishment for purposes other than research

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crohn's Disease Group<br>Patients followed for a Crohn's Disease in consultation or in day hospital aged between 6 and 18 years old. | Other: Blood samples<br>* Blood sample of maximum 20ml (5 tubes of EDTA of 4ml or 5 tubes of EDTA of 2ml and a tube for the conservation of genomic DNA)<br>Other: Biopsies<br>* 5 biopsies (one for each segment of the intestine explored: ileum, right colon, transverse colon left colon and sigmoid) will be taken during the ileocolonoscopy<br>|
| Other: Control Group<br>Patients followed for functional abdominal disorders | Other: Blood samples<br>* Blood sample of maximum 20ml (5 tubes of EDTA of 4ml or 5 tubes of EDTA of 2ml and a tube for the conservation of genomic DNA)<br>Other: Biopsies<br>* 5 biopsies (one for each segment of the intestine explored: ileum, right colon, transverse colon left colon and sigmoid) will be taken during the ileocolonoscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of autophagic flux by western blot. | LC3II/LC3I will be measured by western blot after booking the autophagic flux at different time point. | 1 day (during hospitalization for ileocolonoscopy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of autophagic polymorphisms in pediatric Crohn's disease population | DNA sequencing of polymorphisms reported in the literature as gene mutations susceptibility for Crohn's disease. | 1 day (during hospitalization for ileocolonoscopy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Autophagy, Polymorphism