Separating wheat from chaff in celiac disease

Three protein fragments may trigger immune reactions in intestinal ailment

Three protein fragments are looking like the guilty parties in celiac disease, an intestinal ailment that affects as many as one in 133 people in the United States. These partial proteins, or peptides, are the part of gluten in wheat, rye and barley that triggers the immune systems of celiac patients, damaging the small intestine. An Australian research team reports the new findings in the July 21 Science Translational Medicine.

Pinpointing these peptides has opened the way for development of a therapeutic vaccine that might help celiac patients tolerate these foods. The research team is pursuing that line of work now, led by study coauthor Robert Anderson, a gastroenterologist at the Royal Melbourne Hospital and the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia.

As it is, celiac patients deal with their condition by avoiding wheat, rye and barley.

“This is an impressive and very comprehensive study,” says immunologist Ludvig Sollid of the University of Oslo. “The authors find that most celiac patients make a response to the three gluten peptides.”

That response lies at the heart of the problem. Most people digest these cereals effortlessly, but people with celiac disease have a genetic predisposition that causes an aberrant immune response to gluten. That in turn damages the walls of the small intestine and sabotages their ability to absorb food. Celiac disease can cause painful bloating, diarrhea, constipation, lethargy and other problems. Its genetic underpinnings are poorly understood.

In contrast, the cereal side of the equation is now becoming clearer. Scientists fingered gluten in the 1950s as the celiac trigger, but the gluten protein is complex, and the scanning technology needed to sort out its offending components has become available only recently.

The Australian team put that technology to use. First they gave more than 200 celiac patients in Australia and Britain wheat, barley and rye in foods for three days. This mobilized immune T cells to mount an attack on gluten. The researchers used these T cells to measure the patients’ immune reactions to 2,700 compounds found in gluten. Using the new scanning technology to narrow the field, they found that while dozens of peptides elicited some immune response, three stood apart from the rest. One appears in a type of wheat gluten. Another is found in rye gluten. And a third peptide shows up on certain gluten proteins in all three cereals.

The Australian team has begun an early-stage clinical trial using these peptides in a vaccine that aims to desensitize celiac patients and make them tolerant of the compounds. The group expects to report preliminary safety results later this year.

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