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Diagnosis and prognosis biomarkers: presence and extension of intestinal fibrosis in IBD

Workpackage: WP4

Currently, gold standards to assess the extension and severity of fibrosis in IBD are the histological analysis of intestinal resection after surgery as well as entero-MRI. To date, accurate surrogate biomarkers of intestinal fibrosis are not available. There is therefore a huge unmet need of biomarkers able to assess the presence, severity, extension and evolution of intestinal fibrosis in CD. In this task, the study population will include 2 discovery cohorts: a cross-sectional  population of 50 consecutive CD patients undergoing small bowel surgical resection or stricturoplasty for stenosis due to intestinal fibrosis (group 1) and 150 consecutive patients with CD attending the department of Gastroenterology and having no intestinal fibrosis  evaluated at entero MRI and endoscopy (group 2). All patients included in group 1 will undergo serum biobanking and tissue sampling during the surgery or stricturoplasty. Outcome at M4-M12 of the procedure are assessed using the classification of Rutgeerts. Gold standard for the evaluation of the presence and severity of intestinal fibrosis are entero-MRI and the histological analysis of intestinal resection after surgery in group 1. Gross analysis of resected bowel allows the evaluation of strictures. Sampling of normal and pathological tissues is performed for further studies (fibroblasts culture, proteomic and transcriptomic approaches). Microscopic analysis include evaluation of fibrosis (involvement of submucosa, muscle layers, subserosa) and inflammation. Biomarkers in serum are compared between group 1 and group 2. Biomarkers in group 1 are compared between normal and pathological tissues as well as according to the outcome assessed by the classification of Rutgeerts. In sera (classical ELISA or multiplex assays), the following biomarkers are assessed: CCN2, LOX, endothelin, IL-1, IL-33, IL-4, IL-13, IL-6, IL-21, IL-17, IL-22, IL-23, TNFα, MMP-3, galectin 3, MBL, lysophosphatidic acid, sphingosine-1-phosphate, CXCL-4, MCP-1, MIP1- α, amino terminal propeptide of type III collagen (PIIINP), TIMP-1, hyaluronic acid (constituting the Enhanced Liver Fibrosis (ELF) score), CCL2, CCL3, and CCL20. To find new biomarkers of intestinal fibrosis in human patients with CD, we use a multi-omics approach (including proteomics and transcriptomics) in sera, tissues and/or fibroblasts collected in 20 patients for each group 1 and 2 of patients in collaboration with the platform of proteomic (C. Rolando, CNRS, Lille University) and transcriptomic (M Figeac, Lille University).