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A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84

  • Diagnosis of Autoimmunity
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Abstract

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81 %) of T1DM-CD tested sera, but are detectable also in a fraction (27 %) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.

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Conflict of interest

The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Institute Giannina Gaslini, Genoa, Italy

    Marzia Dolcino & Antonio Puccetti

  2. Department of Pathology and Diagnostics, Section of Immunology, University of Verona, Verona, Italy

    Giovanna Zanoni & Elisa Boccola

  3. Department of Medicine, Unit of Autoimmune Diseases, University of Verona, Verona, Italy

    Caterina Bason, Elisa Tinazzi & Claudio Lunardi

  4. Department of Pediatrics, University of Verona, Verona, Italy

    Enrico Valletta & Giovanna Contreas

  5. Department of Experimental Medicine, Section of Histology, University of Genoa, Genoa, Italy

    Antonio Puccetti

Authors
  1. Marzia Dolcino
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  2. Giovanna Zanoni
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  3. Caterina Bason
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  4. Elisa Tinazzi
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  5. Elisa Boccola
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  7. Giovanna Contreas
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Correspondence to Claudio Lunardi.

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Dolcino, M., Zanoni, G., Bason, C. et al. A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84. Immunol Res 56, 465–476 (2013). https://doi.org/10.1007/s12026-013-8420-0

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  • DOI: https://doi.org/10.1007/s12026-013-8420-0

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