Tuesday, June 13, 2017

Celiac Far More Prevalent

thescientist |  In 2015, gastroenterologist Edwin Liu set to work on a clinical and genetic data set that had been growing for more than 20 years. The data pertained to celiac disease, a lifelong condition involving bouts of severe gastrointestinal distress and other symptoms, triggered by ingestion of gluten proteins that are found in wheat and several other grains. In a two-decade collaboration with researchers at Children’s Hospital Colorado in Denver, Liu’s predecessors and colleagues at the University of Colorado kept track of 1,339 babies born in the city who were deemed at risk of developing the disease due to mutations in celiac-linked genes. The researchers carried out yearly tests to see whether or not the children developed the disease, hoping to better define the risk associated with each of the genetic variants.

Not far into his analyses, however, Liu found something in the data that undermined a much larger assumption in the celiac field. “Usually, when we quote numbers for celiac disease, we’re quoting around 1 percent” prevalence in the US population, he says. But using data from this cohort along with estimated frequencies of each genotype across the Denver metro area to extrapolate the incidence of celiac disease to the general population, Liu found that the true prevalence of celiac disease had to be much greater—more than 3 percent by age 15. “It was a surprise,” he says. “These numbers are much higher than anything else quoted in the U.S.”

Researchers reading the paper, which was published online earlier this year in Gastroenterology,1 were similarly taken aback. “If you look at the rates, it’s frightening,” says Joseph Murray, a celiac researcher at the Mayo Clinic in Rochester, Minnesota. Of course, the statistic could be specific to the Denver cohort, he notes, but it does fit in with similar trends reported both in the U.S. and around the world.

Celiac symptoms, which include abdominal pain and distension, diarrhea and flatulence, nausea, and fatigue, are brought on by ingestion of gluten—a protein complex present in wheat, barley, and rye. Unlike food allergies, which are often primarily mediated by an overreaction of adaptive immune responses such as immunoglobulin E antibody production and mast cell activation, celiac disease engages both innate and adaptive immune pathways, and produces antibodies that target not only gluten, but the body’s own proteins. As a result, the disease is generally considered an autoimmune condition. (See illustration.) Triggered by even tiny amounts of gluten, these immunological attacks lead to T cell–mediated atrophy of the gut wall, which can be characterized via a biopsy of the small intestine for celiac diagnosis (see “Diagnosing Celiac Disease”).

As the use of biopsy and other diagnostic methods have improved in recent decades, celiac disease has become easier to detect. So when the first reports of increasing numbers of celiac cases in the U.S. came out in the early 2000s, many researchers attributed the uptick to progress in disease recognition. But closer scrutiny of the data suggested there was more going on. “We weren’t just better at finding celiac disease,” Murray says. “There was a lot more of it to go around.”