Immunologic Research

, Volume 56, Issue 2, pp 465–476

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

  • Marzia Dolcino
  • Giovanna Zanoni
  • Caterina Bason
  • Elisa Tinazzi
  • Elisa Boccola
  • Enrico Valletta
  • Giovanna Contreas
  • Claudio Lunardi
  • Antonio Puccetti
Diagnosis of Autoimmunity

DOI: 10.1007/s12026-013-8420-0

Cite this article as:
Dolcino, M., Zanoni, G., Bason, C. et al. Immunol Res (2013) 56: 465. doi:10.1007/s12026-013-8420-0

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.

Keywords

Celiac diseaseAutoantibodiesRotavirusGene expression

Supplementary material

12026_2013_8420_MOESM1_ESM.doc (40 kb)
Supplementary material 1 (DOC 40 kb)
12026_2013_8420_MOESM2_ESM.xls (4.3 mb)
Supplementary material 2 (XLS 4439 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Marzia Dolcino
    • 1
  • Giovanna Zanoni
    • 2
  • Caterina Bason
    • 3
  • Elisa Tinazzi
    • 3
  • Elisa Boccola
    • 2
  • Enrico Valletta
    • 4
  • Giovanna Contreas
    • 4
  • Claudio Lunardi
    • 3
  • Antonio Puccetti
    • 1
    • 5
  1. 1.Institute Giannina GasliniGenoaItaly
  2. 2.Department of Pathology and Diagnostics, Section of ImmunologyUniversity of VeronaVeronaItaly
  3. 3.Department of Medicine, Unit of Autoimmune DiseasesUniversity of VeronaVeronaItaly
  4. 4.Department of PediatricsUniversity of VeronaVeronaItaly
  5. 5.Department of Experimental Medicine, Section of HistologyUniversity of GenoaGenoaItaly