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.”
