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Celiac.com 02/10/2008 - Researchers have found a 10mer durum wheat peptide capable of shifting a Th1 gluten-intolerant T cell response to a Th2 gluten-tolerant T cell response in intestinal T cell cultures derived from celiac disease children and incubated with deamidated gliadin peptides. Durum wheat peptides could potentially treat celiac disease by causing celiac disease associated T cells to react tolerantly to gluten. In the study, incubation of the T cell cultures with deamidated gliadin peptides resulted in a significant increase in T cell proliferation and interferon-gamma release. Simultaneous exposure to duram wheat peptides totally abolished the cell proliferation and cytokine release while maintaining an elevated release of interleukin-10 (IL-10). The workings of the immune system are too complex to discuss here in detail. Basically when a "pre-helper" CD4-type T cell is presented with an epitope from an antigen (gliadin), the T cell becomes activated and responds to the stimulus by becoming either a type 1 or type 2 helper T cell which in turn releases different subsets of cytokines. The Th1 path promotes mucosal tissue destruction in celiac disease while the Th2 path initiates proliferation of gluten and tTGase antibodies. Th1 and Th2 cytokines each have properties which act in a feedback loop to suppress, limit, and regulate each other's cytokine secretions, i.e. Th1 cytokines suppress Th2 cytokine secretion and vice vesa. Overactivity of either a Th1 or a Th2 response can result in an autoimmune condition. Researchers theorize that balancing Th1/Th2 response can ameliorate and control symptoms and disease progression in at least some autoimmune diseases. Th1 response includes release of the cytokine interferon-gamma which differentiates and activates macrophages. Th2 response can include the release of IL-10, a cytokine which suppresses inflammation and promotes antigen tolerance. Various molecules have been demonstrated to shift Th1/Th2 response in various autoimmune disorders. In the durum wheat study, the presence of the durum wheat peptide in the gliadin peptide incubated celiac intestinal T cell culture increased Th2 IL-10 release and stopped T cell proliferation and Th1 interferon-gamma release. Hence, this durum wheat peptide may be useful as a celiac disease therapy. How effective this treatment may be is unknown at this time. Below is an example of sodium benzoate being used to shift Th1 to Th2 response in a mouse model of multiple sclerosis which improved symptoms and disease progression when fed to the mice orally. This suggests that the durum wheat peptide could potentially treat celiac disease by simply being administered as an oral supplement. However, if a probiotic bacteria could be genetically engineered to continuously secrete a form of this durum wheat peptide in the gut, this could result in essentially a "cure" for celiac disease if the durum wheat peptide proves effective. ---------- Am J Clin Nutr. 2008 Feb;87(2):415-23. A 10-residue peptide from durum wheat promotes a shift from a Th1-type response toward a Th2-type response in celiac disease. Silano M, Di Benedetto R, Maialetti F, De Vincenzi A, Calcaterra R, Trecca A, De Vincenzi M. Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanita, Rome, Italy. http://www.ajcn.org/cgi/content/abstract/87/2/415 ---------- J Immunol. 2007 Jul 1;179(1):275-83. Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis. Brahmachari S, Pahan K. Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA. http://www.jimmunol.org/cgi/content/abstract/179/1/275 * * *
Celiac.com 02/04/2014 - According to a new article by a team of researchers, not all gluten protein is created equal. That is, not all gluten proteins trigger an immune response in people with celiac disease. The research team included Elma M.J. Salentijn, Danny G. Esselink, Svetlana V. Goryunova, Ingrid M. van der Meer, Luud J.W.J. Gilissen, and Marinus J.M. Smulders. They are variously affiliated with the Plant Research International in Wageningen, The Netherlands, and the Vavilov Institute of General Genetics at the Russian Academy of Sciences in Moscow, Russia. Gluten proteins are the source of peptides that can trigger a T cell reaction in celiac disease patients, leading to inflammatory responses in the small intestine. Various peptides with three major T cell epitopes involved in celiac disease are derived from alpha-gliadin fraction of gluten. Numerous factors are known to influence the immunogenicity of individual gene family members, as alpha-gliadins are encoded by a large multi-gene family and amino acid variation in the celiac disease epitopes. That means that some wheat strains are more likely to trigger celiac disease, and other are less likely. Current commercial methods of gluten detection cannot tell the difference between immunogenic and non-immunogenic celiac epitope variants, and thus cannot accurately measure the overall celiac epitope load of a given wheat strain. Being able to tell the difference between what types of wheat have a lower likelihood to cause or trigger celiac disease is important to commercial wheat growers and producers. The team developed a 454 RNA-amplicon sequencing method for alpha-gliadin transcripts that includes the three major celiac disease epitopes and their variants. They used the method to screen 61 different durum wheat cultivars and accessions. They found a total of 304 unique alpha-gliadin transcripts, corresponding to a total of 171 ‘unique deduced protein fragments’ of alpha-gliadins. They used the numbers of these fragments obtained in each plant to calculate quantitative and quantitative differences between the celiac epitopes expressed in the endosperm of these wheat plants. A small number of wheat plants showed a lower ratios of celiac epitope-encoding alpha-gliadin transcripts, though none were entirely free of celiac epitopes. Dedicated 454 RNA-amplicon sequencing allows researchers to group wheat plants according to the genetic variation in alpha-gliadin transcripts, and to screen for plants which are potentially less likely to trigger or promote celiac disease. The alpha-gliadin sequence database the team constructed will provide an important reference in proteomics analysis regarding the immunogenic potential of mature wheat grains. Source: BMC Genomics 2013, 14:905. doi:10.1186/1471-2164-14-905
Celiac.com 05/08/2007 - One of the strategies for developing alternative therapies for treating celiac disease centers on the identification of antagonist peptides that might inhibit the abnormal immune response caused by gliadin peptides in celiac disease. A recent study published in the journal Pediatric Research indicates that a peptide that occurs naturally in durum wheat may protect against the effects of celiac disease by acting as an antagonist against gliadin peptides associated with abnormal immune response. The study was conducted by a team of Italian researchers made up of Drs. Marco Silano, Rita DiBenedetto, Antonello Trecca, Gioachhino Arrabiato, Fabiana Leonardi, Massimo De Vincenzi. The research team set out to assess the antagonistic effects of 10mer, a decapeptide (sequence QQPQDAVQPF) from the alcohol–soluble protein portion of durum wheat, and to evaluate its prospects for preventing gliadin peptides from activating celiac peripheral blood lymphocytes. The team extracted peripheral blood mononuclear cells from children with celiac disease who tested DQ2-positive, and from a healthy control group. These samples were then incubated with the peptic-tryptic digest of bread wheat gliadin (GLP) and peptide 62-75 from [alpha]-gliadin, both alone and separately with 10mer. PBMC proliferation, release of pro-inflammatory Th1 cytokines interferon-[gamma] and tumor necrosis factor-[alpha], release of immuno-regulatory cytokine IL-10, and analysis of CD25 expression as indexes of lymphocytes activation were performed. Exposure to wheat gliadin peptide and peptide 62-75 from [alpha] gliadin both showed increased activation of lymphocytes. However, the incubation samples with 10mer showed inhibited lymphocyte action. The study indicates that naturally occurring peptide 10mer in durum wheat may protect against lymphocyte activity in patients with celiac disease, and that further study and evaluation of these findings is warranted. Pediatric Research. 61(1):67-71, January 2007.