Study reveals piece in the celiac puzzle
Autoimmune disease trigger possibly found
By Euna Lhee - Sun reporter
July 31, 2008
Maryland researchers have identified a key receptor in the intestine that can trigger celiac disease, and they hope their findings can be applied to other autoimmune disorders, such as Type 1 diabetes and multiple sclerosis.
Celiac disease is a digestive disorder that damages the small intestine and interferes with the absorption of nutrients from food. People with the condition cannot process a protein called gluten - most commonly found in grains such as wheat, rye and barley, but also found in medicines and vitamins.
Common in the general population, celiac disease affects an estimated 2 million Americans, or one out of 133 people, according to the National Institute of Diabetes and Digestive and Kidney Diseases.
In this month's issue of Gastroenterology, University of Maryland scientists wrote that gliadin, the toxic component of gluten for celiac patients, binds to an intestinal receptor called CXCR3. The receptor then releases the protein zonulin, which makes the intestine more permeable.
"We know a lot about celiac disease, but we never understood the question of how the protein gains access in the intestine," said Dr. Alessio Fasano, a gastroenterologist who directs the Center for Celiac Research at the University of Maryland and lead author of the study.
"Further study is needed, but this could allow us to intervene so that less zonulin is released, which may prevent the immune response altogether."
In healthy people, the intestine is permeable only for short periods. But in celiac patients, the effect is longer-term, which may cause a variety of health complications. Eventually, the immune system responds by destroying villi - tiny, fingerlike protrusions lining the small intestine that normally allow the organ to absorb nutrients into the bloodstream.
Because the body's own immune system causes the damage, celiac disease is classified as an autoimmune disorder. Others include diabetes and multiple sclerosis, in which the body attacks the pancreas or the nervous system, respectively.
To treat celiac disease, all that most patients normally have to do is eliminate gluten from their diet. If they don't, however, they can become malnourished, regardless of the quantity of food they eat. They can also suffer from osteoporosis, nerve damage, seizures, chronic diarrhea and anemia. Children may appear thinner than their peers and experience delayed growth.
When his son Matt complained of abdominal pain five years ago, Steve Davis, a WBAL radio sports show host, took the boy to a gastroenterologist, who diagnosed Matt with celiac disease.
Davis immediately put his son on a gluten-free diet, and Matt's stomachaches quickly disappeared. Now 9, Matt eats more dairy products, fruits and vegetables than most of his peers, but he says his favorite food is steak.
"It's kind of embarrassing because my other friends eat regular food, and I need to eat special food," said Matt, who is entering the fourth grade. "The hardest part is going to the grocery store and seeing all this food that looks delicious, that I can't eat."
Matt still enjoys gluten-free chocolate-chip cookies, bagels and muffins, which his father orders by mail from Canada. That can get expensive, Davis says.
"It's a challenge because you need to be cognizant of what your child is eating," said Davis, 42, host of the evening talk show Sportsline with Steve Davis. "If you make a mistake, the ramification down the line is severe."
Davis works actively to promote awareness of celiac disease and raises funds for research. He hopes for a drug that will help celiac patients digest gluten, similar to the Lactaid pill taken by lactose-intolerant people who want to eat dairy products.
Maryland's Fasano is a co-founder of Alba Therapeutics Corp., which is conducting Phase 2 clinical trials of a celiac disease drug called larazotide acetate. It works through another mechanism in the same signaling pathway as CXCR3. The Baltimore biotech company, which provided lab support for the study, estimates the potential worldwide market for a celiac drug at $1 billion a year.
Fasano's next step is to see if the receptor CXCR3 releases abnormal amounts of zonulin in patients with other autoimmune disorders, such as Type 1 diabetes and multiple sclerosis. The intestines may be a port of entry through which the instigators of these diseases may gain access to the body, he said.
Dr. Peter Green, spokesman for the American Gastroenterological Association and director of the Celiac Disease Center at Columbia University, called Fasano's latest study extensive and well-designed. But he said it is still unclear how this research fits into scientists' understanding of all the mechanisms of damage in celiac disease, because it involves various pathways."They've shown this mechanism very well, but we're still figuring out the whole picture," Green said. "And working out the mechanisms will provide a greater potential for drug development."
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