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Laura J. Martin, MD
Feb. 9, 2011 -- Blocking an inflammatory protein called interleukin-15 (IL-15) may help treat the symptoms of celiac disease and prevent the development of celiac disease in certain at-risk people, according to new research in mice published in Nature.
Celiac disease is an autoimmune and inflammatory condition that is triggered by gluten, the protein found in wheat, barley, and rye. When people with celiac disease eat gluten, it triggers an inflammatory response that damages the lining of the small intestine. Symptoms include gas, bloating, cramping, and constipation. People with celiac disease are also at risk for nutritional shortfalls including vitamin B12, vitamin B1 (thiamine), vitamin K, vitamin D, calcium, iron, and folate. Risk factors for developing celiac disease include family history of celiac disease and/or a personal or family history of other autoimmune diseases, including rheumatoid arthritis (RA).
Gluten-free diets are the treatment of choice for celiac disease. Such foods are becoming increasingly available because of the dramatic uptick in rates of celiac disease and other conditions that may respond to gluten-free diets.
In the new study, researchers blocked IL-5 in mice genetically altered to have celiac disease and found that the disease symptoms were reversed, and the mice were once again able to eat gluten.
“We have identified one mechanism by which people lose tolerance to gluten,” says author Bana Jabri, MD, PhD, an associate professor of medicine and pathology and co-director of the Digestive Disease Research Core Center at the University of Chicago. “IL-15 may be a critical element that drives the loss of tolerance to gluten, and we can now think about pathways to block it and potentially develop therapies for celiac disease.”
Medications that block IL-15 are being developed for other inflammatory diseases, including RA.
The new research also shows that retinoic acid, a vitamin-A derivative found in acne treatments such as Retin-A and Accutane, may be complicit in the onset of celiac disease.
“Vitamin A in these patients is a bad idea,” she says. “Patients at risk should be careful about using retinoids." This may even include topical retinoids if they can enter the bloodstream, she says.
Those two molecules act together to promote inflammation, she says. “The vitamin A derivative seems to fuel the IL-15, but if you block IL-15, retinoids are OK,” she says.
“In the U.S., we need to increase awareness and diagnosis of celiac disease because less than 10% of patients are diagnosed,” she says. “A gluten-free diet is currently the treatment of choice, but some patients only respond partially, and it is still socially a handicap."
The race is on to develop new therapies to treat or prevent celiac disease, she says.
“At this point, the new study holds theoretic promise,” says Gerard Mullin, MD, an associate professor of medicine at Johns Hopkins School of Medicine and the director of Integrative Nutrition Services at the Johns Hopkins Hospital in Baltimore.“IL-15 may be a major player in driving the inflammatory response in celiac disease, and if we block it, you can tolerate gluten.
“A drug that blocks IL-15 may be most beneficial in people with really aggressive disease that doesn’t respond to conventional dietary measures,” Mullin says. For people with celiac disease, “today’s day and age is better to live in than 10 years ago due to increased availability of gluten-free foods and gluten-free menu options."
Celiac disease is on the rise in the U.S., he says.
“The prevalence has jumped four to five times since the 1940s, but we are not clear why,” Mullin says. “Many food experts have speculated that it is the way grains are processed here, but we do see it in Italy and other places.”
Diagnosing celiac disease is not always straightforward, he says. Blood tests that look for the presence of certain antibodies are the first step. If the results are positive, many doctors will order a biopsy of the small intestine to confirm the diagnosis. This biopsy can also help assess the degree of damage, but “even the biopsy can miss it,” he says.
Richard Desi, MD, a gastroenterologist at the Melissa L. Posner Institute for Digestive Health and Liver Disease at Mercy Medical Center in Baltimore, says that blocking IL-15 may well help some people with celiac disease.
“This may not be it for everybody, but maybe it can help some people,” he says. “We are starting to understand celiac disease a lot more and diagnose it a lot more. The hope is that we will be able to come up with a treatment that doesn’t just involve a gluten-free diet."
SOURCES:Richard Desi , MD, gastroenterologist, Melissa L. Posner Institute for Digestive Health and Liver Disease, Mercy Medical Center, Baltimore.Gerard Mullin, MD, associate professor of medicine, Johns Hopkins School of Medicine, Baltimore.Bana Jabri, MD, PhD, associate professor of medicine and pathology; co-director, Digestive Disease Research Core Center, University of Chicago.DePalo, R. Nature, 2011, manuscript received ahead of print.
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