Year: 2005
Type: article
Study design: Observational Study
Abstract: Coeliac disease (CD) is a multifactorial, gluten-sensitive enteropathy of unknown pathogenesis that comprises in three stages of development: Marsh I (lymphocytosis), Marsh II (lymphocytosis and crypt hyperplasia), and Marsh III (lymphocytosis and crypt hyperplasia and villous atrophy). Treatment with a gluten-free diet (GFD) normalizes the mucosa of the small intestine of these patients. To define the molecular pathways of CD pathogenesis and the tissue remodeling mechanisms upon treatment with a GFD, we analyzed the expression profiles of 48 CD biopsies taken at different stages of the disease following a GFD and 21 controls. The samples were hybridized in duplo on microarray slides containing >21,000 genes. Data analysis was performed by MANOVA and GeneSpring software. The analysis revealed 158 differentially expressed genes involved in the tissue recovery of CD. The genes could be divided into two groups based on their pattern of expression. The first group comprises 102 genes that show a gradual up-regulated pattern of expression towards mucosa normalization. These genes are implicated in enterocyte differentiation processes and represent the functionality of the duodenum. The second group of genes consists of 56 genes that are mainly related to immunological pathways. Many of these genes are regulated by interferon-gamma and their pattern of expression shows a gradual down-regulation of the immune response after gluten withdrawal. Interestingly, our data do not show changes in expression of genes of previously proposed mechanisms in CD, such as apoptosis, oxidative stress or metalloproteinases pathways. Our results reveal that during the mucosa recovery in CD, there are two opposite processes taking place. There is a gradual release of the immune response and a complementarily up-regulation of genes re-stabilising the normal homeostasis of the mucosa of the small intestine.
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Institutes of Health
OpenAlex ID: W2017612739