title: Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA.
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.
authors.affiliation: Pediatric Research Center, Medical School, University of Tampere, Tampere, Finland.
authors.forename: Essi
authors.initials: E
authors.lastname: Myrsky
authors.forename: Sergio
authors.initials: S
authors.lastname: Caja
authors.forename: Zsofi
authors.initials: Z
authors.lastname: Simon-Vecsei
authors.forename: Ilma R
authors.initials: IR
authors.lastname: Korponay-Szabo
authors.forename: Cristina
authors.initials: C
authors.lastname: Nadalutti
authors.forename: Russell
authors.initials: R
authors.lastname: Collighan
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mongeot
authors.forename: Martin
authors.initials: M
authors.lastname: Griffin
authors.forename: Markku
authors.initials: M
authors.lastname: Mäki
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
authors.forename: Katri
authors.initials: K
authors.lastname: Lindfors
mesh_terms: D001323:Autoantibodies / Q000502:physiology*; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology; D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002448:Cell Adhesion; D004727:Endothelium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D010539:Permeability; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
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