Cause of Celiac Disease Probed in Study

Blocking a factor that can activate the human immune response against intestinal bacteria or certain foods could prevent the development of celiac disease in those most at risk, a University of Chicago study has found.

Scientists point to two chemical signals-interleukin 15 and retinoic acid, a derivative of vitamin A-as triggers for the inflammatory response to gluten, a protein found in many grains that causes celiac disease.

Celiac Disease
Celiac disease is labeled as a digestive disorder associated with malabsorption as well as an abnormal immune reaction to gluten.

Celiac disease is a digestive disorder triggered by the protein gluten.

"We found that having elevated levels of IL-15 in the gut could initiate all the early stages of celiac disease in those who were genetically susceptible, and that blocking IL-15 could prevent the disease in our mouse model," said Bana Jabri, associate professor of medicine and pathology of the University.

"It also demonstrated that in the treatment of inflammatory intestinal diseases, vitamin A and its retinoic acid metabolites are likely to do more harm than good," she said.

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"In a stressed intestinal environment retinoic acid, which was thought to lessen inflammation in the intestine, acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen," the authors note.

Gluten can trigger an autoimmune reaction in the intestines of genetically susceptible people. This prevents the proper absorption of food and nutrients, and causes a variety of gastrointestinal and extra-intestinal symptoms.

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For this study, Jabri and colleagues combined insights and data from celiac disease patients, who had been cared for at the University of Chicago's Celiac Disease Center, with experiments using a mouse model of the disease, developed in her lab.

They knew that many patients with this disease had high levels of Interleukin 15 in their intestines.

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When the researchers increased the levels of this signaling molecule in mouse intestine, the mice developed all the early symptoms of celiac disease. Adding retinoic acid to the mix only made the symptoms worse.

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

The study appeared in the journal Nature.

Source-ANI