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Eliminating the Celiac Disease-triggering Properties of Alpha-Gliadin Peptides in Wheat


Photo: Gluten-free bread--CC-moizissimo

Celiac.com 02/16/2011 - A team of researchers recently set out to establish a universal approach to eliminate disease-triggering properties of alpha-gliadin peptides in celiac disease.

The research team included Cristina Mitea, Elma M. J. Salentijn, Peter van Veelen, Svetlana V. Goryunova, Ingrid M. van der Meer, Hetty C. van den Broeck, Jorge R. Mujico, Veronica Monserrat, Luud J. W. J. Gilissen, Jan Wouter Drijfhout, Liesbeth Dekking, Frits Koning, and Marinus J. M. Smulders.

They are affiliated with the Department of Immunohematology and Blood Transfusion at Leiden University Medical Center, in Leiden, Plant Research International at Wageningen UR, and the Allergy Centre Wageningen, in Wageningen, The Netherlands.

Celiac disease is triggered by an uncontrolled immune response to gluten, a mix of wheat storage proteins that include α-gliadins. Research has shown that α-gliadins contain several major epitopes involved in celiac disease pathogenesis.

Eliminating such epitopes from α-gliadins would be a major step towards eliminating gluten toxicity for celiac disease patients.

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The team analyzed over 3,000 expressed α-gliadin sequences from 11 types of bread wheat to figure out if they encode for peptides that might play a role in celiac disease.

The team synthesized all epitope variants they identified as peptides. They then tested each to see if it bound to the disease-associated HLA-DQ2 and HLA-DQ8 molecules, and if it was recognized by patient-derived α-gliadin specific T cell clones.

For each of the α-gliadin derived peptides involved in celiac disease, the team found several specific naturally occurring amino acid substitutions that eliminate the celiac disease-triggering properties of the epitope variants.

Finally, the team proved at the peptide level that by using systematic introduction of such naturally occurring variations α-gliadins, they can generate genes that no longer encode antigenic peptides. That is, they can create genes in wheat that do not trigger celiac disease.

Their work offers an important contribution for developing strategies to modify gluten genes in wheat so that it becomes safe for people with celiac disease and gluten intolerance.

The findings of the study also provide information for design and introduction of safe gluten genes in other cereals, which would conceivably make them both better in quality, and safe for people with celiac disease.


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2 Responses:

 
Jill
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said this on
21 Feb 2011 9:21:44 AM PDT
I wonder if this new grain will be accepted though since it will be a genetically modified organism (GMO).

 
betsy frahm
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
21 Feb 2011 11:22:57 AM PDT
Keep on trying. I am so grateful that you are doing this research and can't wait till you solve the problem and I can feel happy eating a good old sandwich again!




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^^^^^^ good info, tips and tricks^^^^^^^^^ yes, crumbs will make you sick. also, breathing flour/pancake mix, etc that is in the air because eventually, you're going to swallow some.

Hello I was diagnosed Dec 15 of last year and went totally gluten-free the next day. I actually got worse before I got better - it's a steep learning curve - but now, 4 1/2 months later I'm finally seeing improvement. Hang in there.

Called my GI doctor today to make sure he is going to look at my small intestine and do biopsy for Celiac for my EGD and he is. Thanks for the tip everyone about have to start eating gluten again. The office told me to break my gluten free diet and start eating gluten everyday until my EGD. Here's to being miserable again for a few weeks ???

I can completely relate! The horrible mental effects that I have been living with for years is the absolute worst side effect of eating gluten, HANDS DOWN. Worse than the endless tummy aches, worse than the constant diarrhea, worse than the week long migraines, worse than the daily fatigue and body pain.... I honestly though there was something seriously wrong with me and hated my life because of how I felt mentally. I always felt like I was drowning, not in control of my thoughts, trapped in some unexplained misery. My head was always so cloudy, and I was mad because I always felt so slow and stupid. I would feel so lethargic and sad and empty while at the same time be raging inside, wanting to rip out of my own skin. I was mean, terrible, would snap at the people closest to me for no good reason and just felt like I hated everyone and everything. Think of how crappy you feel when you have a terrible cold and flu - I felt that crappy, but mentally. Some days were really bad, some were mild. I always thought it was because I was getting a migraine, or because I had a migraine, or because I had just overcome a migraine, because I didn't sleep well, because....always a random reason to justify why we have all these weird unrelated symptoms before we get diagnosed. I'm happy to say that I have been gluten-free for about 2 months now and though I am not symptom free, the first thing that improved was my mood. I no longer feel foggy and miserable. For the first time in years, my head is clear, I can actually think, and I feel positive and like I am in control of what's going on in my head. I don't hate the world. I don't spend every day bawled up on the corner of the couch depressed and angry. The release of these horrible symptoms is enough to never make me want to cheat, no matter what I have to miss out on. So insane how a little minuscule amount of a stupid protein can wreck such havoc.

I wanted to collect some of the info on NCGI in one place so that visitors who test negative but may still have an issue with gluten can be directed there. I'll add to this post as I find new links, but feel free to add or contribute anything you think may be of use! Matt --- Useful links: An overview from Alessio Fasano, one of the world's leading researchers on celiac and gluten sensitivity: https://www.youtube.com/watch?v=VvfTV57iPUY Umberto Volta, another leading researcher in the field gives some of the latest findings about NCGI: Presentation slides from Dr Volta's visit to Coeliac UK - NCGS about halfway through A scholarly overview from celiac disease magazine: https://www.researchgate.net/profile/Knut_Lundin/publication/232528784_Non-celiac_Gluten_Sensitivity/links/09e415098bbe37c05b000000.pdf A good overview from a sceptical but fair perspective: https://sciencebasedmedicine.org/a-balanced-look-at-gluten-sensitivity/ Another overview: https://celiac.org/celiac-disease/understanding-celiac-disease-2/non-celiac-gluten-sensitivity-2/ University of Chicago's excellent celiac site's take: http://www.cureceliacdisease.org/category/faq-non-celiac-gluten-sensitivity/ A compelling account in the British Medical Journal from an NCGI patient: http://www.bmj.com/content/345/bmj.e7982 Here's some positive news about a potential new test: http://www.medicaldaily.com/non-celiac-gluten-insensitivity-blood-test-392850 NCGI in children: NCGI and auto immune study: https://www.ncbi.nlm.nih.gov/pubmed/26026392 Also consider: Fodmaps: http://www.kcl.ac.uk/lsm/research/divisions/dns/projects/fodmaps/faq.aspx This Monash study: http://fodmapmonash.blogspot.co.uk/2015/03/the-truth-behind-non-celiac-gluten.html suggested some who think they're reacting to gluten should actually be reducing fodmaps Sibo: http://www.webmd.boots.com/digestive-disorders/small-intestinal-bacteria-sibo