THE ROLE OF TOXIC PEPTIDES AND ENDOPEPTIDASES IN CELIAC DISEASE

Key words: 33-mer peptide, Prolyl endopeptidase, Gliadin peptides

Many gluten peptides elicit T cell-proliferative responses in celiac patients. These peptides are rich in proline and glutamine residues and so extremely resistant to proteolysis. This resistance is related to their toxicity. A 33-mer peptide was identified as the primary initiator of the inflamnmatory response to gluten in celiac disease. In vitro and in vivo studies demonstrated its stability towards breakdown by all gastric, pancreatic and intestinal brushborder membrane proteases. This peptide reacts with tissue-transglutaminase with impressive selectivity and it is a potent inducer of gut-derived human T cells from celiac patients. Homologs of this peptide were found in all food grains that are toxic for celiacs but are absent from all non-toxic foods. The 33-mer peptide is detoxified by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for celiac disease in alternative to the gluten-free diet. A clinical trial to test the efficacy in vivo of endopeptidase added to gluten in preventing its multiform toxicity is ongoing.