Two main inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis (UC) are idiopathic. Environmental factors, infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system result in mucosal inflammation. What events initiate and perpetuate this inflammation? In part two I will discuss immunobiology and pathophysiology.
Epidemiology -- High risk groups for both diseases include northern Europe, the UK, and North America, which is stabilizing. The growth rate in low-incidence areas of southern Europe, Asia and developing countries is on the rise. Disease location and extraintestinal complications are seen to co-localize for disease type, pattern, and extaintestinal disease dependent upon race and ethnic origin.
Genetics -- IBD subtype susceptibilities range from IBD1-9. Currently 12 chromosomes have been identified as being affected. Family history is the largest risk factor, with Crohn's patients have a first degree relative in 2.2-16.2% of cases and IBD in 5.2-22.5% of cases. When a sibling has Crohn's, the risk is even higher. Monozygotic twins demonstrated 37.3% concordance and dizygotic twins 7% for Crohn's. Ulcerative colitis patients demonstrate similar familial distribution patterns with lower percentages. Overall, Crohn's is demonstrated to have more of a genetic contribution than UC, with multiple gene products contributing to the risk.
Biochemistry -- Polymorphisms on chromosome 16 may affect signal transduction, epithelial-cell integrity and carnitine transport in lipid metabolism. Two types of pattern-recognition receptors are TLR and NOD. TLR and NOD interactions with different cell types produce events that are either anti-inflammatory or proinflammatory. Across all populations and diseases, IBD3 is found on chromosome 6. Some mutations may even be protective of Crohn's development. NOD has a CARD domain that interacts with adapter molecules to activate NF Kappa B. TLRs also activate NF Kappa B. NF Kappa B is involved in apoptosis.
Environmental Factors and Lifestyle -- Variation in access to and quality of healthcare, sanitation and hygiene may impair mucosal immune system function and induce immune tolerance, both of which compromise immune tolerance. Psychological stress may impact IBD by involving the nervous system. Typical North American diets, consisting of excess carbs and polyunsaturated fats is associated primarily to Crohn's and contrasts to Asia's low rates where sugar consumption is low. Smoking accelerates the need for surgery in Crohn's while being protective of UC. Bacterial infection has unknown impact upon Crohn's, but impairs handling of microbial antigen. Even appendectomy was shown in epidemiological studies to be protective against UC.
The article is very well written, provides excellent and fine detail in special blocks, pros and cons, hypothetical information and clearly understood figures. I do hope you will take the time to look into the article. I look forward to your questions and comments.
Baumgart, Daniel C., and Simon R. Carding. "Inflammatory bowel disease: cause and immunobiology." The Lancet 369.9573 (2007): 1627-1640.
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