Study Points to Molecular Origins of Celiac Disease
3 protein fragments may drive immune response to gluten in those with genetic predisposition to the disorder
WEDNESDAY, July 21, 2010 (HealthDay News) -- Scientists believe they've identified the molecular triggers of celiac disease, a finding they say could lead to the first drugs to tame the chronic, painful gut disorder.
People with celiac disease are intolerant to the protein gluten, which is found in wheat, barley and rye. Consuming these foods triggers an immune reaction that damages the lining of the small intestine, which can prevent the body from absorbing essential vitamins and nutrients.
Currently, the only treatment for celiac disease is adoption of a gluten-free diet, which means avoiding many types of bread, pasta, cereal and other foods. But gluten contamination in many foods makes it difficult to avoid and leads to long-lasting intestinal damage in some patients, said study senior author Robert Anderson, head of the celiac disease research laboratory at the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia.
Regulating the aberrant immune response to gluten with a drug "would be a much more efficient way of dealing with celiac disease," Anderson said, but an incomplete understanding of how the immune system responds to gluten has prevented researchers from developing such therapies.
Gluten actually consists of many different protein components, and it's been unclear which of these fragments induces the immune response seen in celiac disease.
"You can't design drugs for celiac disease until you know the parts of the gluten that are driving the condition," Anderson explained.
During their investigation, he and his colleagues analyzed immune responses in the blood of more than 200 celiac disease patients after they had consumed meals containing gluten.
The researchers screened the blood samples for responses to thousands of different protein fragments (peptides) found in gluten, and they found that the patients' immune systems seemed to be responding negatively to only three of them.
That suggests that "a very precise trigger is driving the immune response," Anderson said. "The problem is not so much gluten, it's really these three peptides."
The authors also noted that most of the immune response to gluten appears tied to a single type of immune system cell, called the T cell.
The results are published in the July 21 issue of Science Translational Medicine.
According to Dr. Alessio Fasano of the University of Maryland School of Medicine in Baltimore, the evidence is indeed strong that these three protein fragments trigger the celiac immune response, but "I'm not sure that it's the end of the story," he added. It remains possible that the screen didn't catch all the gluten components involved in the immune response, Fasano said.
The findings will also not be relevant to everyone with celiac disease, Anderson added, since his team studied patients with a particular genetic susceptibility to the disease. Although most people with the disease show this genetic background, some do not. Anderson and his colleagues are currently working to identify which gluten proteins induce the immune response in the remainder of celiac patients.
Through Anderson's company, Nexpep, based in Ivanhoe, Australia, the researchers are also conducting phase I clinical trials on a drug based on the three gluten protein fragments they identified. The aim of the drug is to desensitize celiac patients to the offending proteins by presenting them in very controlled amounts. They expect results within the next couple of months.
The current study received funding from Nexpep, the Australian National Health and Medical Research Council, Coeliac UK, the Coeliac Research Fund, and others.
Find out more about celiac disease at the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.