Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation

Gastroenterology. 1999 Mar;116(3):566-72. doi: 10.1016/s0016-5085(99)70178-2.

Abstract

Background & aims: Celiac disease is characterized by disturbed jejunal crypt-villus axis biology with immunoglobulin (Ig) A deposits underlining the epithelium. The aim of this study was to test whether celiac disease serum IgA (reticulin/endomysial autoantibodies) interferes with the mesenchymal-epithelial cell cross-talk.

Methods: Differentiation of T84 epithelial cells was induced with IMR-90 fibroblasts or transforming growth factor beta in three-dimensional collagen gel cultures. The effects of purified celiac IgA and monoclonal tissue transglutaminase antibodies (CUB7402) were studied by adding the antibodies to the cocultures.

Results: Active celiac disease IgA, reactive for tissue transglutaminase, significantly inhibited T84 epithelial cell differentiation (P < 0.001) and increased epithelial cell proliferation (P = 0.024). Similar effects were obtained with antibodies against tissue transglutaminase.

Conclusions: Celiac disease-associated IgA class antibodies disturb transforming growth factor beta-mediated fibroblast-epithelial cell cross-talk in this in vitro crypt-villus axis model. This primary finding indicates that celiac disease-specific autoantibodies may also contribute to the formation of the gluten-triggered jejunal mucosal lesion in celiac disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood*
  • Autoantibodies / isolation & purification
  • Autoantibodies / pharmacology
  • Celiac Disease / blood
  • Celiac Disease / immunology*
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Coculture Techniques
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / immunology
  • Extracellular Matrix / physiology
  • Fibroblasts
  • GTP Phosphohydrolases / immunology
  • GTP-Binding Proteins*
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin A / isolation & purification
  • Immunoglobulin A / pharmacology
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / immunology
  • Reference Values
  • Transforming Growth Factor beta / immunology
  • Transglutaminases / immunology

Substances

  • Autoantibodies
  • Immunoglobulin A
  • Transforming Growth Factor beta
  • transglutaminase 2
  • Transglutaminases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins