Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation.
OBJECTIVE
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.
Halttunen
T
T
Institute of Medical Technology, University of Tampere, Finland.
Mäki
M
M
D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D018920:Coculture Techniques; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts; D020558:GTP Phosphohydrolases / Q000276:immunology; D019204:GTP-Binding Proteins; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology
D001323:Autoantibodies; D007070:Immunoglobulin A; D016212:Transforming Growth Factor beta; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins