Celiac Disease-Specific TG2-Targeted Autoantibodies Inhibit Angiogenesis Ex Vivo and In Vivo in Mice by Interfering with Endothelial Cell Dynamics

PLoS One. 2013 Jun 18;8(6):e65887. doi: 10.1371/journal.pone.0065887. Print 2013.


A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Celiac Disease / immunology*
  • Endothelial Cells / immunology
  • Female
  • GTP-Binding Proteins / immunology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Pathologic / immunology*
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology*


  • Autoantibodies
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins

Grants and funding

This work was supported by grants to Celiac Disease Study Group from the Academy of Finland, the Sigrid Juselius Foundation, the Pediatric Research Foundation, the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (grants 9P033 and 9P020), the Research Fund of the Finnish Coeliac Society, Elna Kaarina Savolainen's fund allocated for the development of cancer treatment, the Hungarian Scientific Research Fund (OTKA K101788), and the European Commission (contract numbers PIA-GA-2010-251506 and PERG08-GA-2010-277049). PET studies were conducted within the Finnish Center of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research supported by the Academy of Finland, the University of Turku, Turku University Hospital, and Åbo Akademi University. This work was supported by EC Marie Curie Research Training Network (MRTN-CT-20010-289964). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.