Celiac anti-tissue transglutaminase antibodies interfere with the uptake of alpha gliadin peptide 31-43 but not of peptide 57-68 by epithelial cells

Caputo Ivana (1) , Barone Maria Vittoria (2) , Lepretti Marilena (1) , Martucciello Stefania (1) , Nista Ivan (2) , Troncone Riccardo (2) , Auricchio Salvatore (2) , Sblattero Daniele (3) , Esposito Carla (1)

1 Department of Chemistry
2 Department of Pediatrics & European Laboratory for the Investigation of Food-Induced Diseases
3 Department of Medical Sciences

Celiac disease is characterized by the secretion of IgA-class autoantibodies that target tissue transglutaminase (tTG). It is now recognized that anti-tTG antibodies are functional and not mere bystanders in the pathogenesis of celiac disease. Here we report that interaction between anti-tTG antibodies and extracellular membrane-bound tTG inhibits peptide 31-43 (but not peptide 57-68) uptake by cells, thereby impairing the ability of p31-43 to drive Caco-2 cells into S-phase. This effect did not involve tTG catalytic activity. Because anti-tTG antibodies interfered with epidermal growth factor endocytosis, we assume that they exert their effect by reducing peptide 31-43 endocytosis. Our results suggest that cell-surface tTG plays a hitherto unknown role in the regulation of gliadin peptide uptake and endocytosis.

Mots clés: tTG; CD; p31-43; p57-68; PBS; PFA; BrdU; EGF; ERK; FBS; M- β-CD; MDC; Transglutaminase; Anti-transglutaminase antibodies; Gliadin peptides; Celiac disease; Endocytosis

Caputo Ivana, Barone Maria Vittoria, Lepretti Marilena, Martucciello Stefania, Nista Ivan, et al.. Celiac anti-tissue transglutaminase antibodies interfere with the uptake of alpha gliadin peptide 31-43 but not of peptide 57-68 by epithelial cells. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, 1802 (9), pp.717. ⟨10.1016/j.bbadis.2010.05.010⟩. ⟨hal-00608996⟩