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Found 10 results

  1. Celiac.com 02/29/2016 - Previous studies have shown that oat proteins trigger an adverse anti-33-mer monoclonal antibody reaction that is proportional to the immune responses in terms of T-cell proliferation. Although there has been some research regarding the impact of these varieties on the adaptive response, researchers still don't know very much about the role of the dendritic cells. A research team recently set out to characterize different oat fractions and to study their effect on dendritic cells from celiac patients. The research team included Isabel Comino, David Bernardo, Emmanuelle Bancel, María de Lourdes Moreno, Borja Sánchez, Francisco Barro, Tanja Šuligoj, Paul J. Ciclitira, Ángel Cebolla, Stella C. Knight, Gérard Branlard and Carolina Sousa. They are variously affiliated with the Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain; the Gastroenterology Unit, Antigen Presentation Research Group, Imperial College London & St Mark′s Hospital, Harrow, United Kingdom; the Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; the INRA UMR-1095, Clermont-Ferrand, France; the Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Food Science and Technology Faculty, University of Vigo-Ourense Campus, Ourense, Spain; the Instituto de Agricultura Sostenible (CSIC), Córdoba, Spain; the Division of Diabetes and Nutritional Sciences, King's College London, Gastroenterology, The Rayne Institute, St Thomas' Hospital, London, United Kingdom; and the Biomedal S.L., Sevilla, Spain. The team first isolated protein fragments from oat grains and then analyzed them using SDS–PAGE. They then characterized several proteins in the prolamin fraction using immunological and proteomic tools, as well as Nano-LC-MS/MS. These proteins were very similar to α- and γ-gliadin, and showed reactive sequences to anti-33-mer antibody, indicating their potential for causing adverse immune reactions. Furthermore, the team found that some of the newly identified oat peptides triggered a range of immune responses on circulating dendritic cells from celiac patients, as compared with healthy controls. This is the first study to show that newly identified oat peptides can trigger a range of stimulatory responses on circulating dendritic cells from celiac patients, which highlights the potential of these oat peptides to trigger adverse immune responses in people with celiac disease. Source: Food & Nutrition Research eISSN 1654-661X
  2. Celiac.com 03/27/2017 - A number of researchers are looking to provide alternative or adjunct treatments to the gluten-free diet in celiac disease. Meanwhile, a number of companies are currently developing a wide variety of such options, ranging from various kinds of enzyme therapies, to treatments that eliminate celiac disease reactions, even to vaccines to inoculate celiac sufferers against their condition, perhaps allowing for full recovery and a return to non-gluten-free eating habits, as desired. At least, that's one dream. More likely will be the development of enzymes or other treatments that offer celiacs varying degrees of protection from gluten ingestion. Most likely, such treatments would be designed to augment an existing gluten-free diet, and to provide protection against moderate gluten-contamination when eating out. One particular enzyme that shows strong potential in breaking down toxic peptides in A-gliadin, the main culprit in celiac reactions, is caricain. A recent paper discusses the scientific principles behind the use of caricain for enzyme therapy. The paper is based on a recent study, in which a team of researchers set out to review the structures of the toxic peptides in A-gliadin for key sequences of amino acids or motifs related to toxicity, especially with respect to digestive difficulties, or immunogenicity. The research team included Hugh J. Cornell and Teodor Stelmasiak. They are affiliated with the RMIT University, School of Applied Sciences, Melbourne, Australia, and with Glutagen Pty Ltd, Maribyrnong, Victoria, Australia. For their study, they first evaluated structures of synthetic A-gliadin peptides shown to be toxic in the fetal chick assay, both before and after digestion with duodenal mucosa from patients in long remission. They also measured synthetic peptides corresponding to the undigested residues, and compared the key amino acid sequences, to see if they might be related to direct toxicity and immunogenicity of the peptides. They found that the smallest toxic peptides from celiac mucosal digestion were octa-peptides, which they found in greater amounts than similar products from normal digestion. One of those peptides corresponded to residues 12-19 of A-gliadin and contained the key motifs PSQQ and QQQP of De Ritis et al., while the other corresponded to residues 72-79, and contained the key motif PYPQ (extending to PYPQPQ). These key motifs have been noted by other workers, especially those investigating immunological activity over the past two decades. Their in undigested residues from celiac mucosal digestion These motifs, along with the greater prevalence of these residues, as compared with residues from normal digestion, supports the basic notions underpinning enzyme therapy for celiac disease. These study also supports the basic scientific merits of research and development of the enzyme caricain to break down gliadin peptides with two different types of toxicity, and thus to potentially benefit people with celiac disease. Source: International Journal of Celiac Disease. Vol. 4, No. 4, 2016, pp 113-120. doi: 10.12691/ijcd-4-4-2 Previous study: NCBI
  3. Celiac.com 12/21/2015 - For people with celiac disease, gluten immunogenic peptides might reveal whether you've been bad or good on your gluten-free diet, and whether or not you have gut damage. In fact, the best way to spot transgressions in the gluten-free diet and incomplete mucosal healing in people with celiac disease might just be to check for gluten immunogenic peptides in their urine. For people with celiac disease, the presence of gluten immunogenic peptides in the urine indicates a break in the gluten-free diet, along with incomplete mucosal healing. How do we know this? Because available methods to determine gluten-free diet adherence couldn't detect occasional gluten ingestion that may cause gut mucosal damage, a team of researchers recently set out to develop a method to assess gluten intake, monitor gluten-free diet compliance in celiac patients, and to correlate those results with mucosal damage. The research team included María de Lourdes Moreno, Ángel Cebolla, Alba Muñoz-Suano, Carolina Carrillo-Carrion, Isabel Comino, Ángeles Pizarro, Francisco León, Alfonso Rodríguez-Herrera, and Carolina Sousa. They are variously affiliated with the Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain, with Biomedal S.L., Sevilla, Spain, with Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío in Sevilla, Spain, with Celimmune, Bethesda, Maryland, USA, and with Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain. For their study, the research team collected urine samples of 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides (GIP) in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIP, along with an LFT reader. They found that, in healthy individuals previously subjected to a gluten-free diet, GIP were detectable in concentrated urines as early as 4–6 hours after single gluten intake, and remained detectable for 1–2 days. The urine assay revealed deviation from a gluten-free diet in about 50% of the patients. Analysis of duodenal biopsies showed that nearly 90% of celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with measurable GIP in urine showed incomplete intestinal mucosa recovery. GIP are easily detected in urine after gluten consumption, enabling a new and non-invasive method to monitor gluten-free diet compliance and deviation. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of celiac patients, as well as for basic and clinical research applications, including drug development. Such tests could be very useful for both doctors and patients looking to monitor gluten-free dietary progress and gut healing in people with celiac disease, to say nothing of research and treatment development. Source: Gut, 25 November 2015. doi:10.1136/gutjnl-2015-310148
  4. Gastroenterology Volume 129, Issue 3, Pages 786-796 (September 2005) Celiac.com 09/14/2005 - Researchers have long thought that the resistance of gliadin prolamines to digestive enzymes is a primary contributor to celiac disease—which leads to the intestinal permeability and inflammation in those who are at risk. Taking prolyl-endopeptidase enzymes (PEP) orally has been proposed and explored as a possible treatment for celiac disease (including extensive research done at Stanford Universitys Celiac Sprue Research Foundation – CSRF). In an effort to determine the feasibility of such a treatment, researchers in France conducted both in vitro (outside a living organism) and ex vivo—using biopsy specimens of active celiac disease patients—studies on the effects of PEP on gliadin peptides. For the in vitro studies the researchers used radio-reverse-phase high-performance liquid chromatography and mass spectrometry to analyze the degradation by PEP of 3H-labeled gliadin peptides 56-88 (33-mer). In the ex vivo studies the researchers added PEP and 3H-peptides together onto the mucosal side of duodenal biopsy specimens that were mounted in Using chambers, and the peptide transport and digestion were analyzed using radio-reverse-phase high-performance liquid chromatography. The results indicate that in both in vitro and ex vivo studies the gliadin peptides were only partly degraded by 20 mu/ml of PEP. This concentration of PEP decreased the quantity of intact gliadin peptides (31-49 and 56-88) that crossed the intestinal biopsy specimens, but did not prevent the intestinal passage of toxic or immunostimulatory metabolites—for this the researchers determined that PEP concentrations of at least 500 mu/ml for at least 3 hours was required to achieve full detoxification of gliadin peptides, and thus prevent intestinal transport of active fragments—unfortunately this finding virtually eliminates PEP as a possible treatment option for those with celiac disease. The researchers conclude optimistically, however: "After prolonged exposure to high concentrations of PEP, the amount of immunostimulatory gliadin peptides reaching the local immune system in celiac patients is decreased. These results provide a basis to establish whether such conditions are achievable in vivo (in living organisms)."
  5. Celiac.com 06/10/2013 - Researchers have known for some time that immunoglobulin G antibodies against deamidated gliadin peptides are about as accurate as tissue transglutaminase and endomysium autoantibodies in diagnosing celiac disease in adults. However, not much is known about their predictive value in infants with a suspected gluten enteropathy. A team of researchers recently set out to determine if antibodies to deamidated gliadin peptides could be an accurate predictor of celiac disease in infants. The research team included S. Amarri, P. Alvisi, R. De Giorgio, M.C. Gelli, R. Cicola, F. Tovoli, R. Sassatelli, G. Caio, and U. Volta. They are affiliated with the Pediatric Unit, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. To test whether deamidated gliadin immunoglobulin G antibodies are more reliable than traditional tests for screening celiac disease in infants, the researchers tested 65 children under 2 years of age for deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium immunoglobulin A, and gliadin immunoglobulins A and G. The group included 42 infants with malabsorption, along with 23 infants as control subjects. Thirty-seven of the 42 children with malabsorption had deamidated gliadin antibodies, associated with tissue transglutaminase and endomysial antibodies in 33, and with gliadin immunoglobulins A and G in 21 and 29, respectively. The team conducted intestinal biopsy in 34 of the 37 children who tested positive for deamidated gliadin antibodies. Thirty-two of the 34 showed villous atrophy consistent with celiac disease, while one of the remaining two had a Marsh 1 and the other showed normal mucosa. The control group showed only gliadin immunoglobulins A (4.3 %) and G (39.1 %). The results showed that deamidated gliadin, tissue transglutaminase and endomysial antibodies were significantly more sensitive for celiac disease than gliadin immunoglobulins G and A. High levels of deamidated gliadin antibodies correlated with severe intestinal damage. For infants, deamidated gliadin antibodies showed a higher diagnostic accuracy for celiac disease than gliadin antibodies. High levels of deamidated gliadin antibodies are good predictors of severe gluten-dependent duodenal damage. Source: J Clin Immunol. 2013 Apr 5.
  6. Celiac.com 10/20/2010 - U.S. doctors and patients looking for accurate early diagnosis of celiac disease now have a state of the art celiac disease assay with a high level of sensitivity and specificity. The US Food and Drug Administration (FDA) has given 510(k) clearance for the first two fully automated gliadin tests featuring deamidated peptides for celiac disease. Manufactured by Phadia US, the tests, EliA GliadinDP IgA and EliA GliadinDP IgG, are designed to be used in conjunct with other laboratory and clinical findings in the early diagnosis of celiac disease. According to Gabi Gross, autoimmune franchise leader for Phadia US, "EliA GliadinDP IgA and EliA GliadinDP IgG will offer physicians who suspect a possible case of celiac disease, antibody tests with the lowest number of false positive results." This means less "unnecessary endoscopies and biopsies," she adds. EliA GliadinDP IgA and EliA GliadinDP IgG will offer antibody tests with the lowest number of false positive results for doctors who suspect a patient has celiac disease. The assays are optional on Laboratory Systems Phadia 100Є and Phadia 250 instruments with features like quick turnaround, monthly calibration, onboard instrument dilution, and a discrete single-well, random-access, nonmicrotiter plate format. Phadia also manufactures other approved CLIA moderately complex assays in the EliA autoimmune product line, including anticardiolipin IgG/IgM, anti-B2-glycoprotein 1 IgG/IgM, cyclic citrullinated peptide, tissue transglutaminase IgA/ IgG, gliadin IgA/IgG, dsDNA, antinuclear antibody screen, and ENA antibodies to the following antigens: Sm, U1RNP, RNP70, Ro, La, Scl-70, CENP, and Jo-1. Source: Medscape
  7. Celiac.com 12/12/2012 - In duodenal biopsy samples from people with active celiac disease, the transferrin receptor, CD71, is up-regulated, and promotes retro-transport of secretory immunoglobulin A (SIgA)-gliadin complexes. To better understand how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides, a team of researchers set out to determine if interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. The research team included C. Lebreton, S. Ménard, J. Abed, I.C. Moura, R. Coppo, C. Dugave, R.C. Monteiro, A. Fricot, M.G. Traore, M. Griffin, C. Cellier, G. Malamut, N. Cerf-Bensussan, and M. Heyman. They are affiliated with the Mixed Research Unit 989 of the National Institute of Health and Medical Research (INSERM UMR989) in Paris, France. For their study, the team evaluated duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. The team used fluorescence-labeled small interfering RNAs against CD71 to transfect Caco-2 and HT29-19A epithelial cell lines. They used flow cytometry, immunoprecipitation, and confocal microscopy to assess interactions among IgA, CD71, and transglutaminase 2 (Tgase2). They then assessed transcytosis of SIgA-CD71 complexes and intestinal permeability to the gliadin 3H-p31-49 peptide in polarized monolayers of Caco-2 cells. To assess physical interplay between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells, the team used fluorescence resonance energy transfer and in situ proximity ligation assays. They co-precipitated CD71 and Tgase2 with SIgA, bound to the surface of Caco-2 cells. They found that SIgA-CD71 complexes were internalized and localized in early endosomes and recycling compartments, but not in lysosomes. In the presence of celiac IgA or SIgA against p31-49, transport of intact 3H-p31-49 increased significantly across Caco-2 monolayers, while soluble CD71 or Tgase2 inhibitors interfered with transport. Once it binds to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apical-basal transcytosis of bound peptides. This mechanism is assisted by Tgase2 and might be involved in the pathogenesis of celiac disease. Source: Gastroenterology. 2012 Sep;143(3):698-707.e1-4. doi: 10.1053/j.gastro.2012.05.051.
  8. 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. 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. Source: PLoS ONE 5(12): e15637. doi:10.1371/journal.pone.0015637
  9. Celiac.com 08/06/2009 - A study by a team of Spanish researchers puts the world on notice that gluten may trigger adverse reactions in both celiacs and non-celiacs alike. The research team was made up of E. Arranz, D. Bernardo, L. Fernandez-Salazar, J. A. Garrote and their colleague S. Riestra, all doctors based in Spain. According to the current medical wisdom, innate immunity to gluten plays a critical role in the development of celiac disease (celiac disease). This innate immune response is caused by a reaction to the ‘toxic’ gluten peptides that is mediated by interleukin (IL) 15, like the 19-mer through a DQ2-independent mechanism, and which causes epithelial stress and triggers the intraepithelial lymphocytes to turn into natural killer (NK)-like cells, which then causes enterocyte apoptosis and a compromised permeability of the cells lining of the gut…and, violà, celiac disease! It is by breaching this lining that immuno-dominant peptides, such as the 33-mer peptide, come into contact with the lamina propria, which triggers adaptive immunity. The innate specific response in celiac disease has been pretty well documented, but until recently, no one had described any differential factors between people with celiac disease and those without. Since the toxic 19-mer triggers its damaging effects through a DQ2-independent mechanism, doctors wondered whether the innate immune response was common in both people with and without celiac disease, and whether the adaptive response is emblematic only of susceptible people with celiac disease. A team of researchers recently set out to determine just that, beginning with biopsies from at least three patients with celiac disease who were observing a gluten-free diet and three patients who are free of celiac disease. The research team consisted of D. Bernardo, L. Fernandez-Salazar, J. A. Garrote and their colleague S. Riestra, all based in Spain. The team applied crude gliadin, the gliadin synthetic 19-mer and deaminated 33-mer peptides to the biopsy tissue after discarding the presence of lipopolysaccharide. They did this at concentrations of 100 mg/ml for 3 hours to mimic what are considered the standard timing and concentration in the digestive tract after a routine meal. The research team then washed the specimens and cultured them for 21 hours in new clean culture medium to assess whether an innate stimulus is reflected by an adaptive response. Here’s some technical jargon: Each sample cultured in basal medium served as an internal control. Innate immune mediators IL15 and nitrites were measured by western blot in the biopsy protein extract along with a Griess reagent system in the 3 h supernatants respectively. mRNA levels of adaptive immunity mediators like signal transducers and activators of transcription (STAT) 1, STAT3, tumour necrosis factor a, interferon (IFN) c, IL23 (p19), IL27 (p28) and IL12 (p35) were determined by real-time polymerase chain reaction using b actine levels as house-keeping. Compared with the basal culture, all of the patients were challenged with the gliadin solution, and all of the patients, both those with and those without celiac disease on a gluten free diet, showed IL15 production, which indicates an immune reaction is taking place. More importantly, the IL15-mediated response in patients without celiac disease was triggered, in three of six cases, by the same toxic 19-mer gliadin peptide and, in five of six cases, by the 33-mer gliadin peptide as in those with celiac disease. Significantly, none of the basal cultures showed this result, though the ‘‘non-toxic’’ immuno-dominant 33-mer did induce an innate response that was un-foreseen. Interestingly, one patient with celiac disease and on a gluten-free diet, and three patients without celiac disease, who were also on gluten-free diets, all showed the IL15 response, which was confirmed by western blot analysis. This discounts an intracellular and non-biologically active IL15 response in patients without celiac disease. The gliadin-challenged patients with celiac disease who were on a GFD, showed increased nitrite levels, which those without celiac disease did not show. Following the biopsy mRNA isolation, only patients with celiac disease showed modifications to what are called adaptive mediators (STAT1, STAT3, IFNc). The basal samples of those celiac patients on a gluten-free diet showed IFNc mRNA levels that were 80 times higher than basal samples of those without celiac disease (p value 0.002), along with a slightly higher production of nitrites (p value 0.052). This appears to be the first time that researchers have described an IL15-mediated innate response to gliadin and gliadin peptides in people without celiac disease, as well as the first time they have described an IL15-mediated innate response to the ‘non-toxic’ deaminated immuno-dominant 33-mer peptide. What this all means is that, for the first time, scientists have documented harmful effects of gluten on people without celiac disease. This hypothesis seems to be born out by the fact that all individuals who took place in the study, both those with and those without celiac disease, showed an innate immune response to gluten, though only those with celiac disease showed an adaptive immune response to gluten. Clearly, before doctors can draw any hard and fast conclusions, they will need to do more studies on larger groups. The research team also suggests that people with celiac disease have a lower threshold for triggering an adaptive TH1 response than do non-celiacs, and that people with celiac disease need to be DQ2 positive. The reason for the differences in threshold levels between celiacs and non-celiacs might be tied to the fact that celiac patients show higher basal levels of immune mediators, such as IFNc mRNA, compared to those without celiac disease. That’s one possibility. The difference in threshold levels might also have to do with some kind of defect in permeability of the gut membrane in those with celiac disease, or even a greater IL15-sensitivity response under equal stimulus, which might be mediated by a higher density of IL15 receptor in patients with celiac disease. Gut 2007;56:889–890
  10. Authors Rivabene R. Mancini E. De Vincenzi M. Source Biochimica et Biophysica Acta - Molecular Basis of Disease. 1453(1):152-160, 1999 Jan 6. Abstract: Coeliac disease (celiac disease) is an inflammatory disorder of the upper small intestine in which gluten acts as an essential factor in its pathogenesis. Although it is generally accepted that cereal protein activation of the immune system is involved in celiac disease progression, a non-immunomediated cytotoxic activity of gliadin-derived peptides on the jejunal/duodenal tract cannot be excluded. In this work, considering that (a) little has been reported about the intracellular metabolic events associated with gliadin toxicity, and ( an important role for free radicals in a number of gastrointestinal disease has been demonstrated, we investigated the in vitro effects of gliadin-derived peptides on redox metabolism of Caco-2 intestinal cells during a kinetic study in which cells were exposed to peptic-tryptic digest of bread wheal up to 48 h. We found that the antiproliferative effects displayed by gliadin exposure was associated with intracellular oxidative imbalance, characterized by an increased presence of lipid peroxides, an augmented oxidized (GSSC)/reduced (GSH) glutathione ratio and a loss in protein-bound sulfhydryl groups. Significant structural perturbations of the cell plasma membrane were also detected. Additional experiments performed by using the specific GSH-depleting agent buthionine sulfoximine provide evidence that the extent of gliadin-induced cell growth arrest critically depends upon the basal redox profile of the enterocytes. On the whole, these findings seem to suggest that, besides the adoption of a strictly gluten-free diet, the possibility for an adjuvant therapy with antioxidants may be considered for celiac disease patients. © 1999 Elsevier Science B.V. All rights reserved. [References: 38]