Celiac Disease Triggered by Intestinal Viruses

Digestive problems, severe inflammation of the small intestine and nutritional deficiencies leading to anemia and osteoporosis force patients of the autoimmune condition celiac disease to follow a strict gluten-free diet for life.

In celiac patients, gluten, a protein contained in many types of cereals, causes the immune system to attack the intestine and the number of people being diagnosed with celiac disease has increased significantly in recent decades and that those affected by the condition are at greater risk of developing other autoimmune diseases; however, less is known about the actual triggers of the disease.

Scientists at the University of Naples Federico II (Italy) and their colleagues analyzed samples of blood serum and 150 small-intestine biopsies from celiac patients and compared them with those of a healthy control group. Serum samples from at least 50 controls (CTR) and 50 celiac disease (CD) patients were tested to detect anti-reovirus antibodies, in a plaque-reduction neutralization assay. Ribonucleic acid (RNA) from duodenal biopsies of 20 CTR and 20 CD patients was tested for interferon-alpha (IFNα), IFN-β and MX Dynamin Like GTPase 1(Mx1), an IFN inducible gene, expression by quantataive polymerase chain reactin (qPCR). The Interferon-induced GTP-binding protein Mx1 (MxA) and interleukin-15 (IL-15) protein expression was evaluated by immunohistochemistry (IHC) in duodenal paraffin-embedded sections.

The team found that a higher number of CD patients showed significantly elevated anti-reovirus serum titers compared to CTR, suggesting that an increased frequency of infections over time occurred in those subjects. An up-regulation of the type-1 IFN pathway was supported by higher levels of Mx-1, IFN-α and IFN-β found in small intestinal biopsies of CD patients compared to controls as well as by the increased MxA protein levels, as assessed by Western blot and IHC shown in the mucosa of CD patients.

Reinhard Hinterleitner, a co-author of the study, said, “Intestinal viruses upset the small intestine and regulatory T lymphocytes can be transformed into pro-inflammatory T lymphocytes as a result. The dendritic cells are also alerted by the infection. If gluten containing food is consumed at the same time as a viral infection occurs, the already alerted dendritic cells also present gluten antigens to the T lymphocytes.” The study was published originally in the April 2016 issue of the journal Gastroenterology.

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University of Naples Federico II