title: Tissue transglutaminase on trophoblast cells as a possible target of autoantibodies contributing to pregnancy complications in celiac patients.
abstract: OBJECTIVE
  Women with celiac disease (CD) are often affected by atypical presentations of the disease associated with reproductive disorders as a main extra-digestive complaint. Here, we analyzed if autoantibodies against tissue transglutaminase (tTG) in sera from CD patients with reproductive disorders could display direct effects through their interaction with tTG expressed on trophoblast cells and phagocytes inducing tissue damage and interfering in the clearance of trophoblast apoptotic bodies.
  
  
  METHODS
  Sera from CD women with reproductive disorders were obtained, and their ability to induce apoptosis of Swan-71 (cytotrophoblast cell line) and to modulate the wound-healing and phagocytes process was tested.
  
  
  RESULTS
  Swan-71 cells expressed tTG and CD sera displayed a significant decrease in trophoblast cell migration and a delay in injury healing on trophoblast cells, compared with those observed with control sera. Moreover, CD sera significantly reduced trophoblast cell proliferation and increased apoptosis levels in comparison with those observed in the control sera. Finally, autoantibodies against tTG interfere in the clearance of trophoblast apoptotic bodies through a mechanism involving MFG-E8 (milk fat globulin-EGF factor 8)-tTG binding.
  
  
  CONCLUSIONS
  The anti-tTG antibodies might contribute to trophoblast damage and disrupt the phagocytosis process of apoptotic bodies that could promote a pro-inflammatory microenvironment.
authors: Immunology Laboratory, School of Sciences/School of Chemistry, Montevideo, Uruguay; EUTM-School of Medicine UDELAR, Montevideo, Uruguay.
authors: Cecilia
authors: C
authors: Sóñora
authors: Guillermina
authors: G
authors: Calo
authors: Laura
authors: L
authors: Fraccaroli
authors: Claudia
authors: C
authors: Pérez-Leirós
authors: Ana
authors: A
authors: Hernández
authors: Rosanna
authors: R
authors: Ramhorst
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism; D014327:Trophoblasts / Q000201:enzymology / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Celiac patients; pregnancy complications; tissue transglutaminase