Dr Jason Tye-Din

Enterovirus infection in early childhood may be a trigger for later coeliac disease in children at increased genetic risk of the condition due to HLA genotypes.

The findings come from a Norwegian study of 220 children who were carrying the HLA genotype DR4-DQ8/DR3- DQ2, conferring increased risk of coeliac disease.

After an average of nearly 10 years of follow up, 25 children were diagnosed with coeliac disease. Each child was then matched to two healthy controls.

Enterovirus was found in 370 (17%) of 2135 stool samples, with 73 children having at least one positive sample. And it was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls – 84 out of 429 (20%) in cases and 129 out of 855 (15%) in controls (adjusted odds ratio 1.49).

Adenovirus was not linked to the development of the disease.

The association was restricted to infections after introduction of gluten, suggesting that the infection itself was the disease trigger.

Writing in the BMJ, the study authors said their results were compatible with a mechanism whereby viral infections may disrupt the mucosal barrier with increased translocation of gluten peptides into the mucosa as the initial event in the loss of tolerance.

“We speculate that enteroviruses may provide a danger signal that activates dendritic cells acting as antigen presenting cells for CD4 positive gluten reactive T cells in the presence of transglutaminase modified gluten peptides,” they wrote.

“Patients with coeliac disease may have enteric barrier disruption before the development of autoantibodies and thus a susceptibility to enterovirus. However, we believe a more plausible explanation is that enterovirus causes impaired barrier function, which in turn increases the risk of coeliac disease.”

And since the HLA-DQ2/DQ8 genotype represents nearly all “genetically susceptible” people, they believe that their findings are likely to apply to a large proportion of those with coeliac disease.

The authors also suggest that identifying specific viruses as triggers may justify preventative strategies.

“If enterovirus is confirmed as a trigger factor, vaccination could reduce the risk of development of coeliac disease,” they conclude.

Commenting on the findings, Dr Jason Tye-Din, Head of the Coeliac Research Lab at the Walter and Eliza Hall Institute (WEHI),  noted that enterovirus was not present in most children who developed coeliac disease, highlighting that other factors are important in disease development.

“The findings support the growing body of information that micro-organisms may be an important trigger of autoimmune disease [but] more research needs to be done to understand the mechanism of how microbes like this virus might cause this effect,” he said.