An enterovirus infection in early childhood could be a trigger for the development of celiac disease in children with increased genetic risk for the disease, according to data published in The BMJ.
Ketil Størdal, of the department of pediatrics at Østfold Hospital Trust and Norwegian Institute of Public Health in Oslo, Norway, and colleagues wrote that previous research has suggested that infections, particularly gastrointestinal infections, could have a role in the development of celiac disease.
“Gastrointestinal infections are common in childhood and may impair the mucosal barrier for transfer of dietary proteins as gluten regardless of the presence of clinical symptoms,” they wrote. “We aimed to test whether the presence of human enterovirus and adenovirus in monthly fecal samples was more common before development of celiac disease antibodies in cases subsequently diagnosed as having celiac disease compared with children not developing the disease.”
Researchers performed a case-control study nested within the Norwegian birth cohort recruited between 2001 and 2007 and followed patients until September 2016. The study comprised 220 children who carried the HLA genotype DR4-DQ8/DR3-DQ2, which signals an increased risk for celiac disease.
They identified enterovirus and adenovirus by analyzing monthly stool samples from 3 months to 36 months and diagnosed celiac disease by testing blood samples taken at months 3, 6, 9, 12 and then annually.
After a mean of 9.9 years, investigators identified 25 children with celiac disease and matched them to two controls each. Enterovirus was found more frequently in samples collected before the development of celiac antibodies in cases compared with controls (adjusted OR = 1.49; 95% CI, 1.07–2.06). This association was limited to infections that were identified after the introduction of gluten and included both commonly detected enterovirus species, Enterovirus A and Enterovirus B. They did not find any association between celiac disease and adenovirus.
Størdal and colleagues wrote that enterovirus could 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.
“Patients with celiac 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 celiac disease,” they wrote. “If enterovirus is confirmed as a trigger factor, vaccination could reduce the risk of development of celiac disease.” – by Alex Young
Disclosures: The authors report no relevant financial disclosures.