Celiac Disease Insights: Clues to Solving Autoimmunity by Alessio Fasano contained so much terrific information that I couldn’t fit it all in one post. Today I will discuss the highlights related to the three causes of celiac disease and the cutting-edge treatment research currently underway.
The Big 3: Factors that Give Rise to Celiac Disease
Susceptibility to celiac disease, and the activation of symptoms involve a combination of environmental, genetic, and immunologic factors: 1) the presence of gluten in the diet 2) a genetically-based predisposition for the immune system to overreact to gluten; and 3) an unusually permeable gut (i.e., “leaky gut syndrome,” but more on that later).
What’s the Issue with Gluten?
Most protein molecules are broken down into to their amino acid components during digestion, but gluten is not well digested by the gut and isn’t broken down like other proteins. There is no known difference between those with and without celiac disease in their ability to break down gluten molecules during digestion.
Repeated exposure to gluten causes the fingerlike structures lining the small intestine (called villi) in those with celiac disease to become chronically inflamed and damaged, leaving them unable to break down food or carry nutrients from the intestine into the bloodstream.
This damage is completely or almost completely reversed and gastrointestinal symptoms are resolved if sufferers stay on a strict gluten-free diet.
The “Celiac Genes”
There are two genes that contribute to a heightened immune sensitivity for gluten, and 95% of people with celiac disease have at least one of them compared to only 30-40% of the general population. Thus, these genes are necessary but not sufficient to cause the disorder.
These genes code for proteins that act as markers to activate the immune system. In people with celiac disease, tissue transglutaminase (TTG), TTG leaks out of damaged intestinal cells in an attempt to heal the surrounding tissue.
TTG also attaches to gluten and causes it to bind with these proteins. This complex is what activates the T cells of the immune system.
T cells, when activated, also release cytokines and chemokines, which ratchet up the immune response. This response would be helpful if you had a bacterial infection, but in the case of gluten, it serves no purpose and, in fact, results in mucosal damage of the small intestine.
Patients with celiac have other genetic abnormalities that include hyperactive immune cells and a tendency to overproduce immune stimulants.
Intestinal Permeability
Although this was controversial at first, researchers now agree that many autoimmune diseases, including celiac disease, diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease, involve increased intestinal permeability.
A protein in humans called zonulin increases intestinal permeability by loosening the complex structure of tight junctions between the cells of the intestine. It is thought that this is the result of the abnormal immune response in those with celiac disease.
Cutting Edge Treatment Research
Dr. Fasano believes that removing any one factor in the celiac disease trinity (the environmental factor, the genetic factor, or the leaky gut) would be enough to stop the disease process. Right now, a strict gluten-free diet is the only way to treat celiac disease because even a small amount of gluten sets off the immune reaction described above. However, adhering to a lifelong gluten-free diet can be very difficult, so researchers are attempting to find other ways of treating celiac disease.
Here are some potential new treatments that are currently being developed:
- drugs to break down gluten peptides completely, which researchers expect would prevent the immune response
- drugs to inhibit TTG, which would intervene in the chain of events that cause the immune response
- interventions to dampen the genetically controlled factors that lead to the oversensitive immune system (though gene therapy has not been explored)
- drugs to block intestinal permeability (the results of pilot studies appear promising)
- gluten-free diet for the first year of life may prolong or prevent the development of celiac disease among high-risk infants
- probiotic treatment
Reminder: The University of Chicago Celiac Disease Center is offering free blood testing on October 10, 2009. Go to www.celiacdisease.net for details.
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