title: Alterations of the intestinal transport and processing of gliadin peptides in celiac disease.
abstract: OBJECTIVE
  The hypothesis of a defect in the intestinal transport and processing of toxic (31-49) or immunostimulant (57-68 and the 33-mer 56-89) gliadin peptides was tested in patients with active celiac disease (ACD), patients with treated celiac disease (TCD), and controls.
  
  
  METHODS
  Using duodenal biopsy specimens mounted in Ussing chambers, we measured electrical resistance, mucosal-to-serosal radiolabeled-peptide fluxes, and peptide processing during transport using radio-reverse-phase high-performance liquid chromatography.
  
  
  RESULTS
  Peptide 31-49 fluxes (24.7 microg x 3 h(-1). cm(-2)) were increased in patients with ACD compared with controls and patients with TCD (12.7 and 12.3 microg x 3 h(-1). cm(-2); P < 0.01). In contrast, no increase was observed for peptide 57-68 or 56-89 (33-mer). Electrical resistance was decreased in patients with ACD versus controls (15.3 vs. 23.9 ohms. cm(2); P < 0.001). Peptide 57-68 was partially degraded by brush-border peptidases in controls but not in patients with celiac disease. However, it was totally degraded after intestinal transport both in controls and patients with celiac disease. Peptides 31-49 and 56-89 were resistant to brush-border peptidases in all groups of patients but were totally degraded during intestinal transport in controls and patients with TCD. In patients with ACD, however, 50% of peptide 31-49 was delivered intact into the serosal compartment and only partial degradation of the 33-mer was observed. These abnormalities were not related to a nonspecific paracellular leakage.
  
  
  CONCLUSIONS
  Our data indicate that gliadin peptides, although poorly or not digested by intraluminal enzymes, can be fully digested by enterocytes in controls and patients with TCD. In patients with ACD, incomplete degradation of the 33-mer and protected transport of the peptide 31-49 might favor their respective immunostimulatory and toxic effects.
authors.affiliation: INSERM EMI 0212, Faculté Necker-Enfants Malades, Paris.
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Celine
authors.initials: C
authors.lastname: Candalh
authors.forename: Christophe
authors.initials: C
authors.lastname: Dugave
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Christophe
authors.initials: C
authors.lastname: Cellier
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Martine
authors.initials: M
authors.lastname: Heyman
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D001706:Biopsy; D002446:Celiac Disease / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D005260:Female; D005903:Gliadin / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010446:Peptide Fragments; D005903:Gliadin; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases