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 output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)3375-85
Number of pages11
JournalCellular and Molecular Life Sciences
Volume66
Issue number20
DOIs
Publication statusPublished - Oct 2009

Keywords

  • celiac disease
  • disease-specific autoantibodies
  • transglutaminase 2
  • vascular permeability
  • RhoA activation

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    Myrsky, E., Caja, S., Simon-Vecsei, Z., Korponay-Szabo, I. R., Nadalutti, C., Collighan, R., Mongeot, A., Griffin, M., Mäki, M., Kaukinen, K., & Lindfors, K. (2009). Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA. Cellular and Molecular Life Sciences, 66(20), 3375-85. https://doi.org/10.1007/s00018-009-0116-1