In celiac disease, the consumption of gluten, which is found in wheat, rye, barley, and some other grains and food products, causes the immune system to erroneously attack the intestine. This leads to inflammation and the symptoms of disease, like abdominal cramping and pain (and in severe cases, malnutrition). Usually, the symptoms stop when patients stop eating gluten, but about 1% of patients don't get relief this way. Even after adopting a restrictive diet, the intestinal inflammation that is a hallmark of the gastrointestinal disorder does not stop. Scientists wanted to know why, and now, a culprit has been identified.
Researchers used single-cell sequencing to learn more about the immune cells in the guts of celiac patients who were not responding to a gluten-free diet. Reporting in Science Translational Medicine, the investigators determined that in some celiac patients, there are 'rogue' immune cells, which carry certain genetic mutations.
"For decades, doctors have struggled to understand why a small proportion of celiac patients do not improve on a strict gluten-free diet," said senior study author Professor Chris Goodnow of the Garvan Institute of Medical Research. "Our research suggests that, in some cases, the disease may be fueled by immune cells that have acquired genetic mutations--something we've never been able to see before."
There are two types of refractory celiac disease, and this is the first time scientists have found a cause for type 1. This work showed that some patients with this type of celiac disease carry genetically mutated immune cells, which have similarities to some cancerous cells. The mutations help the cells grow and survive. They can persist and cause chronic inflammation even when there is no gluten in the diet. They may arise during periods of gluten exposure, the researchers suggested.
The study assessed cells from ten patients, and seven were confirmed to carry these cells. Now, scientists may be able to develop better treatments for this type of celiac disease. Right now, the disease can only be treated by tamping down the entire immune system, which can lead to many other problems.
This work can also help reveal which celiac patients will not benefit from a gluten-free diet, and may eventually lead to new ways to treat these individuals.
Sources: Garvan Institute of Medical Research, Science Translational Medicine