Early viral infection may contribute to celiac development

April 28, 2017

Researchers believe a vaccine could be developed to prevent the formation of celiac disease and possibly other autoimmune disorders.

Early infection with a seemingly innocuous virus may trigger an autoimmune response that could lead to later development of celiac disease, according to a new study that suggests the discovery could result in the creation of a vaccine against the increasingly common disease.

The new study, titled “Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease,” published in Science suggests that the relatively common reovirus may be in part to blame for celiac virus, but researchers believe a prophylactic vaccine could possibly be developed for at-risk individuals.

According to the study, celiac disease results from a specific autoimmune reaction certain individuals have to the peptides in dietary gluten. Increased incidence over the years has suggested that there may be an environmental link in some cases, and infection by several virus types-particularly the reovirus-have been associated with a sort of scarring in the immune system that may lead to later development of celiac disease.

The reovirus typically doesn’t cause significant illness on its own, but researchers found that the individuals they studied with celiac disease had significantly higher antireovirus antibody titers that those without celiac disease, as well as elevated levels of interferon regulatory factor 1-a protein that induces an adaptive immune response and is associated with an increased risk of celiac disease.

Reovirus, and possibly others, were therefore found to elicit proinflammatory responses that could affect immune system homestasis and oral tolerance of food antigens including gluten, according to the report.

Next: Signals of early viral damage

 

Signals of early viral damage

Terence S. Dermody, MD, Vira I. Heinz Professor and Chair of Pediatrics and professor of Microbiology and Molecular Genetics and the University of Pittsburgh School of Medicine, and one of the authors of the study, says the antibodies against reovirus in celiac patients signal early viral damage that may contribute to later celiac development.

 “It’s the first demonstration that a virus can induce loss of tolerance to a dietary antigen, and in particular, we provide evidence that reovirus can trigger loss of oral tolerance and inflammatory immune responses to gluten,” Dermody, who is also physician-in-chief and scientific director at Children’s Hospital of Pittsburgh of UPMC, told Medical Economics. “We show that a virus that is apparently innocuous and cleared from the body can alter in the background in absence of overt disease the way the intestinal immune system sees a dietary antigen.”

The study also provides evidence that a subset of celiac patients have abnormally high antibody titers to reovirus and that those high titers are associated with the transcriptional signature that has been found in mice with reovirus-induced loss of oral tolerance.

If researchers are able to show that reovirus is indeed the cause of celiac disease, this means that a vaccine could be created that may prevent celiac disease in genetically at-risk individuals, Dermody said.

“This study enhances our basic understanding of how the immune system distinguishes between food antigens and intestinal invaders and points a way forward to preventing autoimmune diseases by vaccination,” he said.

Other enteric viruses have been found to affect different pathways, as well, according to the report, such as norovirus being associated with later development of colitis. Recent studies have also identified opportunistic bacterial pathogens that colonize in the small intestine of celiac and alter gluten metabolism.

An editorial accompanying the study suggests that the discoveries outlined by the research team may not only lead to the development of a vaccine, but could have implications for treatment beyond celiac disease.

“The implications of the Bouziat et al., study expand beyond food sensitivities and celiac disease to possibly other autoimmune disorders where the triggering agent is still un- known,” the editorial states. “In the future, new strategies could be implemented to prevent autoimmunity and food sensitivities, through the monitoring and prophylactic intervention of common viral infections, some of which are currently considered clinically irrelevant.”