Viral Infection May Be Immune Trigger in Celiac Disease

According to researchers at the University of Chicago and the University of Pittsburgh School of Medicine, infection with a common strain of viruses belonging to the reovirus family, could cause the immune system to trigger an inflammatory response against gluten. This autoimmune reaction is a hallmark of celiac disease, which can only be managed through strict adherence to a gluten-free diet.

Previous studies have implicated viruses in the development of a number of autoimmune disorders, including type 1 diabetes. According to the researchers, who published their findings in the prestigious journal, Science, these virus-associated diseases could one day be treated and prevented using vaccines.

“This study clearly shows that a virus that is not clinically symptomatic can still do bad things to the immune system and set the stage for an autoimmune disorder, and for celiac disease in particular,” said Dr. Bana Jabri, professor in the Department of Medicine and Pediatrics, vice chair for research in the Department of Medicine, and director of research at the University of Chicago Celiac Disease Center. “However, the specific virus and its genes, the interaction between the microbe and the host, and the health status of the host are all going to matter as well.”

Previous research conducted by Jabri and her colleagues found that a cytokine known as IL-15 is upregulated in the intestinal cells of some patients with celiac disease. While not all patients overexpress this signaling molecule, the researchers found that it has an effect on a patient’s tolerance to gluten.

In the current study, the research team investigated two different reovirus strains and their effect on the immune system. While both genetically-distinct strains produced an asymptomatic infection in mice, only one strain triggered an inflammatory response against gluten, resulting in loss of tolerance to the protein.

“We have been studying reovirus for some time, and we were surprised by the discovery of a potential link between reovirus and celiac disease,” said Dr. Terence Dermody, chair of the Department of Pediatrics at the University of Pittsburgh School of Medicine and physician-in-chief and scientific director at Children’s Hospital of Pittsburgh of UPMC. “We are now in a position to precisely define the viral factors responsible for the induction of the autoimmune response.”

When studying celiac disease patients, the researchers found that they had higher levels of anti-reovirus antibodies in their system, compared to healthy individuals. The patients also showed elevated levels of gene expression of a transcriptional regulator, known as IRF1, which has been implicated in gluten intolerance.

The study investigators postulated that a previous infection with a reovirus could have a lasting effect on patients’ immune systems, causing them to develop an autoimmune response when later exposed to gluten. Because gluten is largely resistant to be being broken down by the digestive system, it’s inherently more immunogenic, even in those without gluten intolerance.

So how can this information be used to help, or even prevent, celiac disease? For Jabri and her team, future vaccination against reoviruses may be best administered during infanthood.

In the US, babies are usually weaned from breastfeeding when they are six months old, and some of their first solid foods often contain gluten. If genetically-predisposed children become infected with a reovirus around the same time as their first exposure to gluten, they could be more likely to develop celiac disease.

“During the first year of life, the immune system is still maturing, so for a child with a particular genetic background, getting a particular virus at that time can leave a kind of scar that then has long term consequences,” said Jabri. “That’s why we believe that once we have more studies, we may want to think about whether children at high risk of developing celiac disease should be vaccinated.”

Celiac disease is relatively common in the US, with an estimated one in 133 individuals suffering from the condition. Some have estimated that only 17 percent of these people have been formally diagnosed with celiac disease, which causes gastrointestinal damage when gluten-containing foods and grains are ingested.