Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for celiac disease

Cristina Mitea ¹, Robert Havenaar ², Jan Wouter Drijfhout ¹, Luppo Edens ³, Liesbeth Dekking ^1* and Frits Koning ¹

¹ Dept of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
² TNO Quality of Life, Zeist, Netherlands
³ DSM Food Specialties, Delft, Netherlands

^* To whom correspondence should be addressed. E-mail: e.h.a.dekking{at}lumc.nl.

Accepted 24 April 2007

Abstract

Background Celiac 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 likely contributes to the immunogenic nature of gluten.

Aims In this study we have determined the efficiency of gluten degradation by a post- proline cutting enzyme, prolyl endoprotease from Aspergillus niger (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 four 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.

Conclusion AN-PEP is capable of accelerating the degradation of gluten in a gastrointestinal system that closely mimics in vivo digestion. This implies that co-administration of AN-PEP with a gluten containing meal might eliminate gluten toxicity, thus offering patients the possibility to (occasionally) abandon their strict gluten free diet

Keywords: Western blot, celiac disease, competition assay, gluten degradation, prolyl endoprotease

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