Does a Virus Trigger Coeliac Disease?

Interesting piece from the IFM today for you – I would have said it is pretty obvious that infection is involved somewhere, if ‘only’ in causing immune dysregulation:

Is a Virus Responsible for Celiac Disease? 

The rise in autoimmune conditions in the developed world has led to questions about whether subclinical infections could play a role in setting the stage for celiac and other autoimmune diseases. Environmental factors are implicated due to the rapidly increasing rates of autoimmune conditions, including celiac disease.¹ Researchers are beginning to identity the factors that could be responsible.
 

One potential trigger is the disruption of immune function due to infection. Subclinical infections with reovirus are common, although researchers aren’t sure exactly how common. In one US study, 50% of children aged five to six showed evidence of reovirus infection.2 Reovirus usually causes few symptoms and is considered relatively harmless.3

A new study provides evidence that subclinical infections may indeed play a role in celiac pathology.⁴ In the first part of the experiment, mice genetically engineered to have celiac susceptibility were injected with a human reovirus. When mice were exposed to gliadin, those that had been exposed to reovirus had a much stronger immune response—two to three times more gliadin antibodies than controls. This suggests that reovirus changed the gastrointestinal immune response, creating a milieu where immune activation was more pronounced. In the second part of the experiment, humans with celiac disease were tested for the presence of reovirus antibodies. Not all of the celiac patients showed immune signatures from reovirus; however, a significantly higher proportion of diagnosed celiacs did show reovirus antibodies when compared to controls.⁴
 
This suggests that even seemingly harmless viral infections may alter immune response and lead to autoimmune conditions like celiac disease. One model for the development of autoimmune conditions involves a triad: genetics, intestinal permeability, and environmental factors.⁵ Reovirus could be one such common environmental factor. Only a few studies have examined potential viral antecedents for celiac. Small correlations have been found, for instance, between respiratory syncytial virus infection in children and celiac disease.⁶ The microbiome also plays a role in gastrointestinal immune response,^7,8 and individuals with celiac are known to have different microbial populations than healthy controls.^7,8,9
 
Reovirus infections are one potential disruptor for immune and microbial homeostasis; other triggers are likely to be implicated in celiac disease pathology in the future. Understanding these antecedents will improve our ability to not only treat these patients but to potentially reduce the prevalence of autoimmune conditions.

References

1. Pagliari D, Urgesi R, Frosali S, et al. The interaction among microbiota, immunity, and genetic and dietary factors is the condicio sine qua non celiac disease can develop. J Immunol Res. 2015;2015:123653. doi: 10.1155/2015/123653.

2. Tai JH, Williams JV, Edwards KM, Wright PF, Crowe JE Jr, Dermody TS. Prevalence of reovirus-specific antibodies in young children in Nashville, Tennessee. J Infect Dis. 2005;191(8):1221-24. doi: 10.1086/428911.

3. Kapikian AZ, Shope RE. Chapter 63: Rotaviruses, reoviruses, coltiviruses, and orbiviruses. In: Baron S, ed. Medical Microbiology. 4th ed. Galveston, TX: University of Texas Medical Branch at Galveston; 1996. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8558/.

4. Bouziat R, Hinterleitner R, Brown JJ, et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017;356(6333):44-50. doi: 10.1126/science.aah5298.

5. Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005;2(9):416-22. doi: 10.1038/ncpgasthep0259.

6. Tjernberg AR, Ludvigsson JF. Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection. Dig Dis Sci. 2014;59(7):1502-08. doi: 10.1007/s10620-014-3046-1.

7. Verdu EF, Caminero A. How infection can incite sensitivity to food. Science. 2017;356(6333):29-30. doi: 10.1126/science.aan1500.

8. Cheng J, Kalliomäki M, Heilig HG, et al. Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease. BMC Gastroenterol. 2013;13:113. doi: 10.1186/1471-230X-13-113.

9. Cenit MC, Olivares M, Codoñer-Franch P, Sanz Y. Intestinal microbiota and celiac disease: cause, consequence or co-evolution? Nutrients. 2015;7(8):6900-23. doi: 10.3390/nu7085314.