Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease.
OBJECTIVE
Tissue transglutaminase (tTG) autoantibodies are markers of celiac disease, and the enzyme is required for several crucial biological processes. The aim of this study was to determine whether these autoantibodies are involved in the pathogenesis of the mucosal lesion typical of celiac disease.


METHODS
Using rhodamine-conjugated phalloidin staining, we evaluated whether tTG antibodies, both commercially available and cloned from patients with celiac disease, cause cytoskeletal changes in Caco-2, MCF7, and NIH 3T3 cells. We monitored cell levels of bromodeoxyuridine incorporation to determine whether tTG autoantibodies are able to induce NIH 3T3 fibroblasts and epithelial mucosal cells into S phase.


RESULTS
Treatment with tTG antibodies caused a dose-dependent increase of membrane ruffling in Caco-2, MCF7, and NIH 3T3 cells. It also dose-dependently induced G(0)-synchronized NIH 3T3 fibroblasts into S phase but did not affect the rate of apoptosis. Similarly, tTG antibodies induced S-phase entry of epithelial cells in cultured intestinal biopsy specimens from patients with celiac disease. They did not affect biopsy specimens from patients without celiac disease.


CONCLUSIONS
Our results suggest that tTG autoantibodies per se, by interacting with the extracellular membrane-bound transglutaminase, may play an important role in epithelial cell proliferation in celiac disease.
Barone
Maria V
MV
Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
Caputo
Ivana
I
Ribecco
Maria T
MT
Maglio
Maria
M
Marzari
Roberto
R
Sblattero
Daniele
D
Troncone
Riccardo
R
Auricchio
Salvatore
S
Esposito
Carla
C
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000627:therapeutic use*; D001706:Biopsy; D001973:Bromodeoxyuridine; D018938:Caco-2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002446:Celiac Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D019204:GTP-Binding Proteins; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins; D011503:Transglutaminases / Q000276:immunology*
D000199:Actins; D001323:Autoantibodies; D011994:Recombinant Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D001973:Bromodeoxyuridine