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Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA

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Abstract

Celiac disease is characterized by the presence of specific autoantibodies targeted against transglutaminase 2 (TG2) in untreated patients’ serum and at their production site in the small-bowel mucosa below the basement membrane and around the blood vessels. As these autoantibodies have biological activity in vitro, such as inhibition of angiogenesis, we studied if they might also modulate the endothelial barrier function. Our results show that celiac disease patient autoantibodies increase endothelial permeability for macromolecules, and enhance the binding of lymphocytes to the endothelium and their transendothelial migration when compared to control antibodies in an endothelial cell-based in vitro model. We also demonstrate that these effects are mediated by increased activities of TG2 and RhoA. Since the small bowel mucosal endothelium serves as a “gatekeeper” in inflammatory processes, the disease-specific autoantibodies targeted against TG2 could thus contribute to the pathogenic cascade of celiac disease by increasing blood vessel permeability.

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Acknowledgements

The authors wish to thank Mr. Jorma Kulmala for technical assistance. The Celiac Disease Study Group has been financially supported by the Research Council for Health, the Academy of Finland, the Juselius Foundation, the Paediatric Research Foundation, the Competitive Research Funding of the Pirkanmaa Hospital District, the Research Fund of the Finnish Celiac Society, the Hungarian Scientific Research Fund (OTKA K61868), and the European Commission (contract number MRTN-CT-2006-036032).

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Authors and Affiliations

  1. Pediatric Research Center, Medical School, University of Tampere, 33014, Tampere, Finland

    Essi Myrsky, Sergio Caja, Cristina Nadalutti, Markku Mäki, Katri Kaukinen & Katri Lindfors

  2. Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Zsofi Simon-Vecsei

  3. Heim Pál Children’s Hospital, Budapest, and Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Ilma R. Korponay-Szabo

  4. School of Life and Health Sciences, Aston University, Birmingham, UK

    Russell Collighan & Martin Griffin

  5. X Link, Nottingham, UK

    Alexandre Mongeot

  6. Department of Pediatrics, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland

    Markku Mäki

  7. Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland

    Katri Kaukinen

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  1. Essi Myrsky
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Correspondence to Katri Lindfors.

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Myrsky, E., Caja, S., Simon-Vecsei, Z. et al. Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA. Cell. Mol. Life Sci. 66, 3375–3385 (2009). https://doi.org/10.1007/s00018-009-0116-1

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  • DOI: https://doi.org/10.1007/s00018-009-0116-1

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