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Celiac Disease: A Look into its Pathogenesis



Celiac.com 07/25/2011 - Celiac disease, according to estimates, affects approximately three million Americans and as of yet, 97% haven't been correctly diagnosed. As staggering as these statistics are, celiac disease remains largely poorly understood by the medical community. It's no wonder, given its lack of research as compared with other autoimmune disorders. However, there is research being actively conducted in the U.S. and internationally in a quest to understand the pathogenesis, or the cause and development of the disease. With this information, more about celiac disease, diagnosis, prevention, and treatment can come to light.

According to the Canadian Celiac Association (CCA), the pathogenesis of celiac disease consists of three factors: "genetic, environment and immunologic." With regard to genetics, the CCA points out that more than 97% of celiac patients have the genetic markers HLA DQ2 and/or HLA DQ8. Celiac disease is now known to be a hereditary disease. The Canadian Celiac Association tells us that "first-degree and to a lesser extent second-degree relatives are at higher risk of having unrecognized celiac disease."

Next, is the environmental "trigger," as Dr. Alessio Fasano, professor of pediatrics, medicine and physiology at the Center for Celiac Research at the University of Maryland School of Medicine, calls it. This is gluten, a protein found in wheat, barley, and rye. According to the Canadian Celiac Association, sometimes severe physical stressors can also trigger the immunologic reaction to gluten that is characteristic to celiac disease. Such sources of stress include pregnancy, infection, surgery, or even severe emotional stress.

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In his article, "Surprises from Celiac Disease," published in Scientific American, Dr. Fasano describes a different triad of factors involved in the pathogenesis of the disease. The first two factors are the ‘'trigger" of gluten, which sets off the immune response, and the genetic predisposition, as previously described. Fasano proposes that "other genes are likely to be involved as well, but these additional culprits may differ from person to person."

The third factor, according to Fasano's research is an "unusually permeable gut." In fact, the author proposes that these three factors also underlie the pathogenesis of other autoimmune diseases, with of course triggers and genetic elements unique to those particular diseases. Fasano tells us that most non-celiacs have "tight junctions [that] 'glue' intestinal cells together." On the other hand, in celiac patients, these links come apart, resulting in a small intestine from which pieces of gluten leak into the tissue and stimulate a response from immune cells. Fasano's research regarding this third factor of pathogenesis offers hope of new prevention and treatment methods. He says, "Treatments that reduced leakiness could potentially ease not only celiac disease but also other autoimmune disorders involving unusually permeable intestines."

This research into the leaky gut of celiacs can explain a question that has been perplexing researchers regarding the disease's pathogenesis: Why do some people not develop celiac disease until later in life? According to Dr. Fasano, this issue could be associated with the microbes in the digestive tract. The microbicrobial population varies among individuals and groups and even over the course of one's life.

"Apparently they can also influence which genes in their hosts are active at any given time," he says. "Hence, a person whose immune system has managed to tolerate gluten for many years might suddenly lose tolerance if the microbiome changes in a way that causes formerly quiet susceptibility genes to become active." Should this prove true, we may be able to prevent or treat celiac disease with probiotics.

A better understanding of the pathogenesis of celiac disease is certainly needed, but as of yet, researchers seem to be on their way to developing a full picture of what is involved in the origin and onset of the disease. By raising awareness and allocating more funding to celiac pathogenesis research, we may find ourselves with the ability to delay or even prevent the disease or with a new treatment option.

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2 Responses:

 
george
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said this on
01 Aug 2011 7:05:43 AM PST
Excellent review.

 
JoAnne
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said this on
01 Aug 2011 8:25:45 PM PST
Thank you for taking the time to help support and educate all of us who are affected by this condition.




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That is very helpful. Thank you so much.