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Gastroenterology. 2003 Sep;125(3):696-707.

Alterations of the intestinal transport and processing of gliadin peptides in celiac disease.

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1
INSERM EMI 0212, Faculté Necker-Enfants Malades, Paris.

Abstract

BACKGROUND & AIMS:

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.

PMID:
12949716
[Indexed for MEDLINE]
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