Is Celiac Disease Linked to Rotavirus Protein? By Roy Jamron

Celiac.com 09/29/2006 - A new study identified a peptide which causes an immune reaction in a majority of active celiac disease patients but no such reaction in any celiac disease patients on a gluten-free diet. Antibodies to this celiac peptide also recognize and bind to the rotavirus protein VP-7 and cause increased intestinal permeability. Antibodies to VP-7 produced in rabbits also increase intestinal permeability. The celiac peptide also binds to Toll-like receptor 4 and activates monocytes (white blood cells active in innate immunity.) IgA and IgG antibodies to rotavirus protein VP-7 are present in a majority of celiac disease patients and to a much lesser percent of the general population. This suggests VP-7 may be involved in the pathogenesis of celiac disease through a molecular mimicry mechanism.

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"In our attempt to clarify the pathogenesis of celiac disease, we screened a random peptide library with pooled sera of patients affected by active disease after a pre-screening with the sera of the same patients on a gluten-free diet. We identified a peptide recognized by serum immunoglobulins of patients with active disease, but not by those of patients on a gluten-free diet. This peptide shares homology with the rotavirus major neutralizing protein VP-7 and with the self-antigens tissue transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like receptor 4. We show that antibodies against the peptide affinity-purified from the sera of patients with active disease recognize the viral product and self-antigens in ELISA and Western blot. These antibodies were able to induce increased epithelial cell permeability evaluated by transepithelial flux of [3H] mannitol in the T84 human intestinal epithelial cell line. Finally, the purified antibodies induced monocyte activation upon binding Toll-like receptor 4, evaluated both by surface expression of activation markers and by production of pro-inflammatory cytokines."

"Our findings show that in active celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the viral protein VP-7, suggesting a possible involvement of rotavirus infection in the pathogenesis of the disease, through a mechanism of molecular mimicry. Moreover, such antibodies recognize self-antigens and are functionally active, able to increase intestinal permeability and induce monocyte activation. We therefore provide evidence for the involvement of innate immunity in the pathogenesis of celiac disease through a previously unknown mechanism of engagement of Toll-like receptor 4."