title: Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease.
abstract: BACKGROUND
  Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten.
  
  
  OBJECTIVE
  This study determined the efficiency of gluten degradation by a post-proline cutting enzyme, Aspergillus niger prolyl endoprotease (AN-PEP), in a dynamic system that closely mimics the human gastrointestinal tract (TIM system).
  
  
  METHODS
  Two experiments were performed. In the first, a slice of bread was processed in the TIM system with and without co-administration of AN-PEP. In the second, a standard fast food menu was used. Samples of the digesting meals were taken from the stomach, duodenum, jejunum and ileum compartments at time zero until 4 hours after the start of the experiment. In these samples the levels of immunogenic peptides from gliadins and glutenins were assessed by monoclonal antibody-based competition assays, Western blot analysis and proliferation T-cell assays.
  
  
  RESULTS
  AN-PEP accelerated the degradation of gluten in the stomach compartment to such an extent that hardly any gluten reached the duodenum compartment.
  
  
  CONCLUSIONS
  AN-PEP is capable of accelerating the degradation of gluten in a gastrointestinal system that closely mimics in-vivo digestion. This implies that the co-administration of AN-PEP with a gluten-containing meal might eliminate gluten toxicity, thus offering patients the possibility of abandoning (occasionally) their strict gluten-free diet.
authors.affiliation: Department of Immunohematology and Blood Transfusion, E3-Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Mitea
authors.forename: R
authors.initials: R
authors.lastname: Havenaar
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: L
authors.initials: L
authors.lastname: Edens
authors.forename: L
authors.initials: L
authors.lastname: Dekking
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D001234:Aspergillus niger / Q000201:enzymology*; D002446:Celiac Disease / Q000201:enzymology / Q000209:etiology*; D005260:Female; D005983:Glutens / Q000378:metabolism*; D006801:Humans; D008297:Male; D018448:Models, Immunological; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000502:physiology*; D013270:Stomach / Q000201:enzymology*
chemical_list: D005983:Glutens; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases