Celiac disease is an autoimmune disorder triggered by gluten, a protein in wheat, barley, rye and spelt. Currently, the only treatment available is the adoption of a lifelong gluten free diet, which is made particularly challenging due to the prevalence of wheat in western diets. It is an excellent example of environmental challenge meeting gene susceptibility, and is a unique example of how exclusion of an environmental trigger can resolve the symptoms.
“Celiac disease has become much more common in the last 50 years, and we don’t know why,” said Dr Joseph Murray of Mayo Clinic “…Obviously human genes haven’t changed, but something has changed in our environment to make this disease more common....”
Key Ideas:
- Celiac disease (CD) is an autoimmune disorder triggered by ingestion of gluten, a major protein in wheat, rye, barley and often oats.
- Research into the root causes indicates that the disorder develops when a person exposed to gluten also has a genetic susceptibility to CD and an unusually permeable intestinal wall.
- Essentially the same trio—an environmental trigger, a genetic susceptibility and a “leaky gut”—seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD may also ameliorate other conditions.
- CD is an immune mediated pathology that may be managed not simply through exclusion of the antigen – gluten, but also through the improvement of digestion, reduction of gut permeability, support or mucosal IgA (the gut's immune system)
CD and gluten intolerance represent distinct situations in which local tissue damage in the gut may manifest a wide range of illnesses elsewhere, supporting the notion that many illnesses have an origination in the GI tract
Why Is Gluten So Tough To Handle?
There are two unique features to gluten that may partly explain its ability to trigger an immune response.- They have a high content of proline in the gluten proteins, that are hard to break down using our natural proteases in the gut lumen.
- The gluten fragments are good substrates for the enzyme TransGlutamase (TG2) converting glutamine residues to glutamate. This increases the ability of the gluten peptides to bind to the genetically inherited molecules HLA-DQ2 or HLA-DQ8.
References
1. Fasano A. Surprise from celiac disease. Scientific American August 2009.2. Shan,L Et al. Structural Basis for Gluten Intolerance in Celiac Sprue. Science 297, 2275-2279. 2002
3. Arentz-Hansen H, Körner R, Molberg O, Quarsten H, Vader W, Kooy YM, Lundin KE, Koning F, Roepstorff P, Sollid LM, McAdam SN.The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase.J Exp Med. 2000 Feb 21;191(4):603-12.
4. Round JL, Mazmanian SK., The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009 May;9(5):313-23
5. http://www.nleducation.co.uk
No comments:
Post a Comment