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Gluten Peptide Research Advancing Immunotherapy for Celiac Disease

Celiac.com 04/24/2009 - Currently, one of the more promising areas of celiac disease research looks to be in peptide-based therapies. One of the keys to creating an effective peptide-based therapy for celiac disease lies in identifying the gluten peptides that trigger intestinal T cell responses when people with celiac disease consume wheat, rye, or barley.

A team of Italian researchers recently set out to do just that. The team was made up of A. Camarca, R.P. Anderson, G. Mamone, O. Fierro , A. Facchiano, S. Costantini, D. Zanzi, J. Sidney, S. Auricchio, A. Sette, R. Troncone, and C. Gianfrani. Their efforts were supported by the Institute of Food Sciences-National Research Council, Avellino, Italy. Their research carries strong implications for a peptide-based therapy in celiac disease.

Presently, several gluten peptides are known to be active in celiac disease. The identification of additional gluten peptides eliciting intestinal T cell responses is critical for designing a successful peptide-based immunotherapy for celiac disease.

In their study, the research team assessed the recognition profile of gluten immunogenic peptides in adult HLA-DQ2(+) celiac patients. They did so by creating several lines of polyclonal, gliadin-reactive T cells from jejunal mucosa. They then tested for both proliferation and IFN-gamma production in reaction to 21 peptides from wheat glutenins and alpha-, gamma-, and omega-gliadins.  They then conducted a magnitude analysis of the IFN-gamma responses to determine the spectrum of individual peptide activity, and to rank them accordingly.

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Notably, 12 of the 14 patients responded to a different array of peptides. All alpha-gliadin stimulatory peptides mapped the 57-89 N-terminal region, thus affirming the importance of the known polyepitope 33-mer, although  only 50% of subjects recognized 33-mer.

By contrast, 11 of 14 celiac subjects, nearly 80%, responded to gamma-gliadin peptides. A 17-mer variant of 33-mer, QLQPFPQPQLPYPQPQP, posessing only a single copy of DQ2-alpha-I and DQ2-alpha-II epitopes, displayed the same potency as 33-mer in triggering intestinal T cell responses.

One particular peptide from omega-gliadin, QPQQPFPQPQQPFPWQP, though structurally related to the alpha-gliadin 17-mer, is a separate epitope and activated in 5 out of 14 subjects.

The team's data reveal that intestinal T cells respond to a wide array of peptides, and that this heterogeneity  emphasizes the relevance of gamma- and omega-gliadin peptides in celiac disease pathogenesis. Their findings indicate that, in DQ2(+) celiac patients, the most active gluten peptides are alpha-gliadin (57-73), gamma-gliadin (139-153), and omega-gliadin (102-118).


J Immunol. 2009 Apr 1;182(7):4158-66.

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2 Responses:

 
Gerald Jones
Rating: ratingfullratingemptyratingemptyratingemptyratingempty Unrated
said this on
02 May 2009 2:26:04 PM PDT
Way too technical. The only people who can understand that is the people doing the research.

 
Fred Martin
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated ( Author)
said this on
07 May 2009 3:45:43 PM PDT
Good article. From nearly nearly everything I've read, enzymes look very promising for treating celiac disease.




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Hi Could a mod please move this post: and my reply below to a new thread when they get a chance? Thanks! Matt

Hello and welcome Firstly, don't worry about it but for ease your post (and hopefully my reply) will probably be moved to its own thread. That will make it easier for others to see it and reply and also help Galaxy's own thread here on track and making sense. The antibodies that the celiac tests look for can drop very quickly, so... maybe? Celiac is difficult to test for, there are different tests and sometimes someone doesnt test on one but does on the other. If you can get a copy of the tests and post it here the community may be able to help explain the results. It may have shown damage to the villi, the little tendrils in your intestine that help you extract nutrients from your food. Celiac is one, but not the only, way in which they can get damaged leading to a vast number of potential symptoms and further making diagnosis a tricky proposition. Definitely, there's a connection. Here's a page that explains it in detail: https://stomachachefree.wordpress.com/2012/03/21/liver-disease-in-celiacs/ Fantastic It sounds as if your doctors were happy to diagnose you on the basis of the endoscopy? It may be then that you've found your answer. I hope so, you've clearly had a rotten and very scary time. I'm sure with the positive reaction to the diet you want to go on and get healthy, but I would only add that you should discuss this with your doctors, because they may want to exclude other potential causes if they've not confirmed celiac at this point. Check out the advice for newly diagnosed here: To your family I'd simply say that celiac is a disease of the autoimmune system, the part of our body that fights diseases and keeps us safe. In celiac people the autoimmune system see's the gluten protein found in wheat, barley, or rye grains as a threat to the system and it produces antibodies to attack it and in doing so attacks it's own body as well. It's genetic in component so close family members should consider a test if they have any of the many symptoms. There's roughly 1 person in 100 with celiac but most of them don't know it and are risking getting or staying sick by not finding out. There's further info for them and you here: https://www.celiac.com/gluten-free/announcement/3-frequently-asked-questions-about-celiac-disease/ I'm going to ask a mod to move your post and my reply to a new thread, but wanted to give you an answer first The good news is you've found a great site and there will be lots of support for you here. You've also got 'lucky' in that if you're going to have an autoimmune condition, celiac is a good one Most react really well to the gluten free diet and you will hopefully have much more healing to come! Best wishes Matt

Please share what was so difficult about starting your account.

I'm new here so please forgive me if I'm in the wrong forum. But I could use some clarity and input.. So I'll try to make my story brief as possible? So about 8 months ago I began itching uncontrollably and after going to the Dr for labs she found my liver enzymes were 5x what they should be and was referred to a gastro Dr. Gastrointestinal Dr ran multiple scans, blood work over the next 2 months and referred me to teaching hospital with a " tumor board" apparently I had a mass within my bile ducts that was blocking bile from liver. Was given a grim diagnosis of rare cancer and told would be dead within the year. Then had an endoscopy done to get tissue of the mass and for some reason it had partially resolved and was no longer blocking bile duct. At this point they could not find and cancerous cells. So fast forward 3 months I'm still in pain and had another endoscopy and the biopsy taken showed high possibility of celiacs. The blood work was negative for celiac but after the grim cancerous diagnosis I had been unable to eat for 2 weeks or so and so I'm not sure if that would have skewed the labs?. How could the biopsy show high possibility of celiac? And had anyone heard of celiac causing inflammation in the bile ducts? I have been gluten-free for 6 weeks and have been feeling remarkably better pain in the upper right quadrant is less, and migraines ( I have had for my whole life) have lessened. So all this to say I don't understand celiacs and how to explain it to family. Or how all of a sudden this happens. Ask if anyone can shed any insight I would appreciate it. Blessings

Thank you for taking the time for sharing that info. Don't we have the best disease ever! There's got to be a better way to cut down the scarring. Yes, I've scratched till it bleed. Can't help it. It's like having a bunch of mosquito bites. Yes, only gluten free now. Still have bursts, so probably am being exposed to gluten. Will need to stop dapsone soon. Good luck with your situation.