Exploration of the Activity of DNA Located Outside of Cellular Nucleus to Amplify Inflammation in Inflammatory Bowel Disease in Children Through Biological Pathway Cyclic GMP-AMP Synthase (cGAS) - Stimulator of Interferon Genes (STING) (ROXANE)

Centre Hospitalier Régional d'Orléans

Status: Completed

Conditions: Ulcerative Colitis; Inflammatory Bowel Diseases; Crohn Disease

Treatments: Procedure: Coolonic biopsies; Biological: Blood and fecal samples

Study type: Interventional

Funder types: Other

Identifiers

NCT05916274

CHRO-2023-01

Details and patient eligibility

About

Frequency of Inflammatory Bowel Diseases in children (IBD)-Crohn's disease (CD), Ulcerative colitis (UC) is constantly increasing. Pediatric-onset IBD represent a different nosological entity (from adult IBD) because of their major inflammatory activity, their significant anatomical extent and their stenotic and/or fistulizing character sometimes from diagnosis. Intestinal lesions are due to dysregulation of the intestinal immune system but the cause is unknown. The investigators hypothesize that extranuclear DNA participates in the amplification of the inflammatory response at the intestinal and blood levels during pediatric IBD through the cGAS-STING pathway. The investigators will analyse blood and fecal samples, and colonic biopsies issued from ill children and control participants on age of 6 to 17 years. The investigators think that this study will provide a better understanding of the mechanisms involved in pediatric IBD, assess the place of the cGAS-STING pathway, identify potential biomarkers of pediatric IBD and new potential therapeutic targets based in particular on the inhibition of the cGAS-STING pathway.

Full description

Inflammatory Bowel Diseases in children (IBD)-Crohn's disease (CD), ulcerative colitis (UC) are severe pathology that can affect the entire digestive tract. Their annual incidence is however constantly increasing.

IBD are complex multifactorial pathologies whose cause is still unknown today. IBD occurs on a predisposing genetic background in the presence of exogenous factors and alteration of the intestinal microbiota. Intestinal lesions are due to dysregulation of the intestinal immune system with increased secretion of pro-inflammatory cytokines at the expense of anti-inflammatory cytokines.

Pediatric-onset IBD represent a different nosological entity (from adult IBD) because of their major inflammatory activity, their significant anatomical extent and their stenotic and/or fistulizing character sometimes from diagnosis. Their impact is not only individual (growth retardation, puberty delay, psychological disorders) but also family/parental, school and social. These particularities justify that biomedical research focuses on it in a more specific way.

Extracellular and extranuclear DNA (enDNA) play a major role in innate immunity by stimulating pro-inflammatory responses and activating type I interferon production. The pro-inflammatory action of enDNA is mediated by enzyme cGAS, protein STING, toll-like receptor 9 (TLR9), and the inflammasome complex NLRP3.

The investigators hypothesize that enDNA participates in the amplification of the inflammatory response at the intestinal and blood levels during pediatric IBD through the cGAS-STING pathway. They also hypothesize that there are links between the cGAS-STING pathway and other pathways involved in pediatric IBD such as NOD2 and Autophagy. The investigators will analyse blood and fecal samples, and colonic biopsies issued from ill children and controls on age of 6 to 17 years. The investigators think that this study will provide a better understanding of the mechanisms involved in pediatric IBD, assess the place of the cGAS-STING pathway, identify potential biomarkers of pediatric IBD and new potential therapeutic targets based in particular on the inhibition of the cGAS-STING pathway.

Enrollment: 40 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants aged from 6 years inclusive to 17 years inclusive

• Boys and girls

• Presenting an IBD or suspicion of IBD

• Requiring a colonoscopy for diagnosis or follow-up or other reason (abdominal pain, diarrhoea, rectal bleeding, weight loss) not confirming the diagnosis of Crohn's disease or Ulcerative Colitis

• Active IBD if:

  • CD: PCDAI score >5 and CRP>20mg/L and faecal calprotectin> 400 µg/g
  • UC: PUCAI score>10 and faecal calprotectin>250 µg/g

• IBD in remission if:

  • CD: PCDAI score<5 and CRP<20mg/L and faecal calprotectin<400 µg/g
  • UC: PUCAI score <10 and faecal calprotectin < 250 µg/g

• Patients and their parents who gave their consent to participate in the study

Exclusion criteria

• Refusal of the participant and/or one of his two parents
• Body weight less than or equal to 20 kg
• Blood hemoglobin level less than or equal to 9 g/dl
• Refusal or contraindication to general anesthesia
• Co-existing severe chronic pathology and/or treatment that could interfere with the results of the study; example: trisomy 21, treatment with growth hormone etc.
• Protected person (under guardianship or curatorship)
• Person under legal protection
• Person not affiliated to a social security scheme
• Pregnant or breastfeeding woman

Trial design

Primary purpose: Health Services Research

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Patients with samples

Other group

Description:

Blood and fecal samples, and colonic biopsies will be analysed and compared between 3 groups of participants :1/ Active IBD; 2/Inactive IBD; 3/Controls "non-IBD".

Treatment:

Biological: Blood and fecal samples

Procedure: Coolonic biopsies