Immune imbalance in gut may trigger celiac disease

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People who have high levels of an immune system compound called Interleukin-15 may be primed to develop celiac disease, a digestive disorder that keeps sufferers from eating foods like cereal, pasta, cookies and beer.

Blocking this compound in mice helped reverse the disease, U.S. researchers said on Wednesday.

Vitamin A and retinoic acid, a byproduct of vitamin A used in the acne treatments Retin-A and Roche’s former acne drug Accutane, may exacerbate the problem, acting as a trigger for the inflammatory response, the team said.

The findings, published in the journal Nature, suggest that an imbalance of compounds like Interleukin 15 that regulate the immune system could be an underlying cause of food allergies.

“If there is a disregulation in the intestinal environment, this alone can explain how you can lose tolerance to some food items,” Dr. Bana Jabri of the Digestive Disease Research Core Center at the University of Chicago, who led the study, said in a telephone interview.

“It is a first time a pathway has been identified,” she added.

Celiac disease is caused by an abnormal immune response to gluten, a protein found in wheat, rye, barley and other foods.

It occurs in about 1 percent of the population, and can lead to severe health problems including anemia, poor bone health, fatigue and weight loss.

To study it, the team first had to recreate the disease in mice. They knew that many people with celiac disease had high levels of Interleukin-15 in their intestines.

When they increased levels of this immune system compound in mice, they developed all the early symptoms of celiac disease. Adding retinoic acid to the mix only made the symptoms worse, causing inflammation and tissue damage.

When they blocked IL-15, however, the sick mice reverted to normal and were once again able to tolerate gluten.

“We still don’t understand why Interleukin-15 is disregulated,” Jabri said, but she said having mice that develop the disease will allow the team to study potential treatments.

Drugs that block IL-15 are already being studied in patients with rheumatoid arthritis, another inflammatory disease, and Jabri said she thinks they may be useful in celiac disease as well.

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By Julie Steenhuysen

CHICAGO

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