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.
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).
Research
Moderators: Rosie, Jean, CAMary, moremuscle, JFR, Dee, xet, Peggy, Matthew, Gabes-Apg, grannyh, Gloria, Mars, starfire, Polly, Joefnh
Hi Dee,
Thanks for the information. It's good to see that researchers are working on the problem, and making progress. Apparently, there are a lot of reactive peptides yet to be discovered, and with so much variation in patient responses, it may be extremely difficult to resolve the problem by this approach. Still, the fact that they're making progress, is promising.
Dr. Fasano's proposed solution, (a pill to suppress the production of zonulin), is already well into the FDA trial stage, so it may be the first on the market. If other research continues, though, we may eventually have several different products to try, and if that happens, surely one of them will work for most of us.
Thanks for posting that.
Love,
Tex
Thanks for the information. It's good to see that researchers are working on the problem, and making progress. Apparently, there are a lot of reactive peptides yet to be discovered, and with so much variation in patient responses, it may be extremely difficult to resolve the problem by this approach. Still, the fact that they're making progress, is promising.
Dr. Fasano's proposed solution, (a pill to suppress the production of zonulin), is already well into the FDA trial stage, so it may be the first on the market. If other research continues, though, we may eventually have several different products to try, and if that happens, surely one of them will work for most of us.
Thanks for posting that.
Love,
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.