Pathoph ysiology

Genetics In 2001 the first susceptibility gene for Crohn’s disease (CD) (IBD1) was identified. This encodes for a product (NOD2 or CARD15), the CD variant of which is associated with increased intestinal permeability in both CD patients and their unaffected relatives. It is also associated with ileal and fibro-stenosing diseases in Western populations. The mechanism of the permeability changes is uncertain but the CD variant of NOD2 impairs the secretion of antibacterial peptides (defensins) which help contain the bacteria that penetrate the intestinal wall. Subsequently, many other possible candidate genes have been identified. TLR4, which encodes for proteins involved in bacterial recognition, has recently been associated with CD in several populations, as have the IL23R gene in both CD and UC and ATG16L1 and IGRM in CD. The latter genes encode proteins that control autophagy, which is a major defense against intracellular pathogens such as mycobacteria and salmonella. These observations support the central hypothesis that the principal abnormality in irritable bowel disease (IBD) patients is the dysfunction of the intestinal epithelial barrier separating the lumen of the gut from the milieu intérieur.