Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease.
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.
Mitea
C
C
Department of Immunohematology and Blood Transfusion, E3-Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Havenaar
R
R
Drijfhout
J Wouter
JW
Edens
L
L
Dekking
L
L
Koning
F
F
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*
D005983:Glutens; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases