Pathogenesis of inflammatory bowel disease IBD

The inflammatory bowel disease is chronic inflammatory disease of gastrointestinal tract that include Crohn’s disease and ulcerative colitis.

Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs responsible for intestinal homeostasis use diverse intracellular and intercellular networks to promote immune tolerance, inflammation or epithelial restitution.

Complex interfaces integrate local host and microbial signals to activate appropriate effector programs selectively and even drive plasticity between these programs. In addition, genetic studies and mouse models have emphasized the role of genetic predispositions and how they affect interactions with microbial and environmental factors, leading to pro-colitogenic perturbations of the host commensal relationship.

Dr Sandra Kim Named Director of Inflammatory Bowel Disease

Dr. Kim, also associate professor of Clinical Pediatrics at The Ohio State University College of Medicine, comes from the University of North Carolina, Chapel Hill where she served as a pediatric gastroenterologist and an assistant professor in the Division of Gastroenterology. During her tenure, she worked extensively in resident and medical student education on a local and statewide level in addition to holding numerous leadership roles with the Crohn’s and Colitis Foundation of America (CCFA).

Her clinical and research interests focus on pediatric inflammatory bowel diseases, including adolescent transitioning and quality improvement in pediatric IBD and translational research investigating the bacterial and genetic influences in IBD. Her research has been funded by the National Institutes of Health and the CCFA.

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Pathogenesis of inflammatory bowel disease

Over the past 15 years, a wide variety of candidate genes have been studied. Most associations identified between specific candidate genes, including major-histocompatibility-complex loci, and inflammatory bowel disease have not been reproducible, have not shed new light on pathogenesis, or have not facilitated diagnosis

1 . However, substantial progress has now been made with the use of the less biased approach of genome-wide screening with microsatellite DNA markers. Detailed mapping of chromosome 16 has recently resulted in the identification of a gene responsible, at least in part, for this linkage

2 . This gene encodes a cytoplasm protein designated NOD2 (also referred to as CARD 15 [caspase activation and recruitment domain]), which is expressed in macrophages and may serve as a so-called pattern-recognition receptor for bacterial lipopolysaccharide, perhaps regulating nuclear factor-κB(NF-κB) activation and macrophage apoptosis. European and North American patients with Crohn’s disease, including those without a family history of inflammatory bowel disease, are more likely to have variants of NOD2 than are persons without Crohn’s disease. Paradoxically, these NOD2 variants appear to result in reduced macrophage activation of nuclear factor- B in response to lipopolysaccharide. Persons who are homozygous for variant NOD2 may have a 20-fold or more increase in susceptibility to Crohn’s disease, with a particular predilection for ileal disease

3 . Heterozygotes are also at increased risk. However, fewer than 20 percent of patients with Crohn’s disease are homozygous for these NOD2 variants. A putative locus associated with early-onset Crohn’s disease appears to be present on chromosome 5 in the vicinity of genes encoding a variety of cytokine receptors.

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