Cellular and Molecular Life Sciences

, Volume 66, Issue 20, pp 3375–3385 | Cite as

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

  • Essi Myrsky
  • Sergio Caja
  • Zsofi Simon-Vecsei
  • Ilma R. Korponay-Szabo
  • Cristina Nadalutti
  • Russell Collighan
  • Alexandre Mongeot
  • Martin Griffin
  • Markku Mäki
  • Katri Kaukinen
  • Katri LindforsEmail author
Research Article


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.


Celiac disease Disease-specific autoantibodies Transglutaminase 2 Vascular permeability RhoA activation 



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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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Essi Myrsky
    • 1
  • Sergio Caja
    • 1
  • Zsofi Simon-Vecsei
    • 2
  • Ilma R. Korponay-Szabo
    • 3
  • Cristina Nadalutti
    • 1
  • Russell Collighan
    • 4
  • Alexandre Mongeot
    • 5
  • Martin Griffin
    • 4
  • Markku Mäki
    • 1
    • 6
  • Katri Kaukinen
    • 1
    • 7
  • Katri Lindfors
    • 1
    Email author
  1. 1.Pediatric Research Center, Medical SchoolUniversity of TampereTampereFinland
  2. 2.Department of Biochemistry and Molecular Biology, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  3. 3.Heim Pál Children’s Hospital, Budapest, and Department of Pediatrics, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  4. 4.School of Life and Health SciencesAston UniversityBirminghamUK
  5. 5.X LinkNottinghamUK
  6. 6.Department of PediatricsTampere University Hospital, Medical School, University of TampereTampereFinland
  7. 7.Department of Gastroenterology and Alimentary Tract SurgeryTampere University Hospital, Medical School, University of TampereTampereFinland

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