Long-term and acute effects of gliadin on small intestine of patients on potentially pathogenic networks in celiac disease
- 9 October 2009
- journal article
- research article
- Published by Informa UK Limited in Autoimmunity
- Vol. 43 (2), 131-139
- https://doi.org/10.3109/08916930903225229
Abstract
Celiac disease (CD) is a complex, immune-mediated intolerance to gliadin that develops in genetically susceptible individuals. Although the main driving force of the disease is an aberrant autoimmune response, several other pathogenic mechanisms, many still unidentified, are also involved. In order to describe at a network level the alterations provoked by a gliadin insult on the intestinal mucosa of patients, we compared the expression profiles of biopsies from 9 active and 9 treated patients (long-term effects of gliadin), and of 10 biopsies from gluten-free diet treated patients that were incubated in vitro with or without gliadin (acute effects) and integrated significantly altered transcripts into potentially pathogenic biological processes. Using information on Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms represented among the differentially expressed genes, we observed important dysfunction in several complex networks, including those related to cell–cell communication, intracellular signaling, ubiquitin–proteasome system, cell cycle/apoptosis and extracellular matrix. The reconstruction of the role of these biological networks in the development of the intestinal lesion in CD provides a comprehensive picture of key events that contribute to the disease, and could point towards novel functional candidates that might be potential therapeutic targets or responsible for genetic susceptibility.Keywords
This publication has 66 references indexed in Scilit:
- Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4Genes & Immunity, 2007
- Genome-wide linkage analysis of 160 North American families with celiac diseaseGenes & Immunity, 2006
- Celiac Disease—Sandwiched between Innate and Adaptive ImmunityHuman Immunology, 2006
- Genetics in coeliac diseaseBest Practice & Research Clinical Gastroenterology, 2005
- A functional variant of IFNγ gene is associated with coeliac diseaseGenes & Immunity, 2004
- Genetic association of coeliac disease susceptibility to polymorphisms in the ICOS gene on chromosome 2q33Genes & Immunity, 2004
- No Association of CTLA4 Gene With Celiac Disease in the Basque PopulationJournal of Pediatric Gastroenterology and Nutrition, 2003
- HLA‐DRB1 and MHC class 1 chain‐related A haplotypes in Basque families with celiac diseaseTissue Antigens, 2002
- CTLA-4 gene polymorphism is associated with predisposition to coeliac diseaseGut, 1998
- Genome Search in Celiac DiseaseAmerican Journal of Human Genetics, 1998