Cellular and Molecular Life Sciences

, Volume 66, Issue 20, pp 3375–3385

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 Lindfors
Research Article

DOI: 10.1007/s00018-009-0116-1

Cite this article as:
Myrsky, E., Caja, S., Simon-Vecsei, Z. et al. Cell. Mol. Life Sci. (2009) 66: 3375. doi:10.1007/s00018-009-0116-1

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.

Keywords

Celiac diseaseDisease-specific autoantibodiesTransglutaminase 2Vascular permeabilityRhoA activation

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
  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