In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes.

摘要: Background Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are typical serological marker in patients active disease, and may disappear during gluten-free diet treatment. Involvement of infectious agents innate immunity has been suggested but never proven. Molecular mimicry one the mechanisms that links infection autoimmunity. Methods Findings In our attempt clarify pathogenesis celiac we screened random peptide library pooled sera affected after pre-screening same on diet. We identified recognized serum immunoglobulins not those This shares homology rotavirus major neutralizing protein VP-7 self-antigens tissue transglutaminase, human heat shock 60, desmoglein 1, Toll-like receptor 4. show against affinity-purified from recognize viral product ELISA Western blot. These were able induce increased epithelial cell permeability evaluated transepithelial flux [ 3 H] mannitol T84 intestinal line. Finally, purified induced monocyte activation upon binding 4, both surface expression markers production proinflammatory cytokines. Conclusions Our findings subset anti-transglutaminase IgA VP-7, suggesting possible involvement through mechanism molecular mimicry. Moreover, such functionally active, increase activation. therefore provide evidence for previously unknown engagement