| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INFLAMMATION/IMMUNITY/MEDIATORS
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden; and 2DSM Food Specialties, Delft, The Netherlands
Submitted 20 January 2006 ; accepted in final form 7 May 2006
Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4–5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.
immune response; T cell
This article has been cited by other articles:
|
|
 |
|
  M. De Angelis, A. Cassone, C. G. Rizzello, F. Gagliardi, F. Minervini, M. Calasso, R. Di Cagno, R. Francavilla, and M. Gobbetti Mechanism of Degradation of Immunogenic Gluten Epitopes from Triticum turgidum L. var. durum by Sourdough Lactobacilli and Fungal Proteases Appl. Envir. Microbiol., January 15, 2010; 76(2): 508 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T L Freitag, S Rietdijk, Y Junker, Y Popov, A K Bhan, C P Kelly, C Terhorst, and D Schuppan Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice Gut, December 1, 2009; 58(12): 1597 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Tennyson, S. K. Lewis, and P. H. R. Green Review: New and developing therapies for celiac disease Therapeutic Advances in Gastroenterology, September 1, 2009; 2(5): 303 - 309. [Abstract] [PDF]
|
|
|
|
|
|
C Mitea, R Havenaar, J W. Drijfhout, L Edens, L Dekking, and F Koning Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease Gut, January 1, 2008; 57(1): 25 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H.R. Green and C. Cellier Celiac Disease N. Engl. J. Med., October 25, 2007; 357(17): 1731 - 1743. [Full Text] [PDF]
|
|
|
|
|
|
C. G. Rizzello, M. De Angelis, R. Di Cagno, A. Camarca, M. Silano, I. Losito, M. De Vincenzi, M. D. De Bari, F. Palmisano, F. Maurano, et al. Highly Efficient Gluten Degradation by Lactobacilli and Fungal Proteases during Food Processing: New Perspectives for Celiac Disease Appl. Envir. Microbiol., July 15, 2007; 73(14): 4499 - 4507. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
