When patients with celiac disease consume foods containing gluten — a protein present in wheat, barley and rye — their immune systems send out an alarm, triggering a response that can damage their intestines and prevent them from absorbing certain nutrients.
Now, scientists have pinpointed the culprits most responsible for this harmful reaction: three small fragments within the gluten protein that spark chaos in the gut.
This knowledge may lead to better diagnosis of the disease and to the development of new therapies, the researchers say. Currently, the only treatment is for patients to remove all gluten-containing foods (such as bread, pasta, pizza and cookies) from their diets.
"You can't come up with rational approaches to dealing with celiac disease — either diagnosis, treatment or prevention, unless you know what's causing the disease," said study author Bob Anderson, a celiac disease researcher at the Walter and Eliza Hall Institute in Victoria, Australia. "This is the beginning of a much more informed rational approach to dealing with immune and allergic disease by knowing exactly what it is that's driving the disease response," he told LiveScience.
The results are published today in the journal Science Translational Medicine.
Troublesome peptides
For most dieters, eating forbidden foods will set them back from reaching their goals, but for those with celiac disease such mistakes can be graver. The reaction from consuming gluten eventually can lead to deficiencies in essential vitamins. In children, the result can mean stunted growth, according to the Mayo Clinic. About 150,000 people in the United States are diagnosed with the disease, but the actual number affected might be closer to 3 million, according to Anderson.
Although gluten's role in celiac disease was discovered 60 years ago, scientists are still looking for specific gluten fragments — sequences of a dozen or so amino acids (building blocks of proteins such as gluten) — that set off this immune reaction.
Anderson, and fellow researchers recruited more than 200 celiac disease patients for their study. Participants ate servings of bread, rye muffins or boiled barley for three days. Six days after the experiment started, the researchers drew blood samples.
They tested the samples to see how strongly immune cells in the blood reacted to more than 2,700 different gluten peptides (relatively short chains of amino acids). Ninety of the peptides elicited some response, and three in particular generated the biggest reaction.
"These three components account for the majority of the immune response to gluten," Anderson said.
While researchers had hypothesized that the immune response seen in celiac patients was only to a few peptides, the current work is the first real data to support this idea, said Daniel Leffler, director of clinical research at the Celiac Center at Beth Israel Deaconess Medical Center in Boston, Mass.
"I think [the findings] are a significant step forward," he said. "There's really been not that much done on defining which peptides people with celiac disease do and do not respond to," especially for the peptides in rye and barley gluten, he said.
"It really does make our understanding of potential ways to target those therapeutically much easier," he said.
Future therapies
Therapies based on the study results are already under way at a biotechnology company co-founded by Anderson.
Nexpep Pty. Ltd., based in Australia, is working to develop a treatment based on the idea that people with an allergy can be desensitized to the substance they are allergic to by consuming small amounts of it. A few studies have supported the idea; for instance, small studies have suggested exposing children with milk allergies to increasing doses of milk can increase their tolerance.
In the case of celiac disease, exposing patients to small amounts of the three peptides may allow them to better tolerate gluten, the researchers say. The researchers have already completed a clinical trial which involved injecting 34 patients with the three peptides, Anderson said. Data from the trial still needs to be analyzed.
Anderson notes there is evidence to suggest the immune system can change its response to gluten. In the last 60 years, the number of people diagnosed with the disease in the United States has increased 5-fold, according to Anderson.
"Something is changing in the enviornment, the genes haven't changed, but the way that the immune system is handling gluten is obviousluy changing, he said. "So there is a plasiticity about the immune response causing celiac disease."
"I guess we're optimistic that you can reverse whatever the environment is doing to cause the increase in celiac disease by deliberate approaches to strengthen the toleraence of the immune reponse with these peptides," he said.
Leffler thinks the findings might also help with the development of so-called protease therapies — therapies that aim to treat celiac disease by breaking down gluten.
Anderson is director of Nexpep. Several of the researchers are shareholders and serve as consultants.
This article was updated Wednesday at 8:15 pm ET.
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