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Celiac.com 12/03/2024 - Understanding celiac disease has advanced significantly over recent years. From novel treatments to groundbreaking insights into the immune system’s response to gluten, these research breakthroughs are paving the way for new therapies and more accurate diagnoses. Here are five recent advances you’ll want to know about if you or someone you know is affected by celiac disease. 1. Exploring the Gut-Brain Connection in Celiac Disease Scientists have long recognized the importance of the gut-brain connection, and it’s now a major focus in celiac research. Celiac disease doesn’t just affect the digestive system; it’s also linked to neurological symptoms like anxiety, depression, and brain fog. Recent studies show that inflammatory markers in the bloodstream may cross the blood-brain barrier in people with celiac disease, leading to brain inflammation. This discovery has opened the door to new ways of treating neurological symptoms in those with celiac disease. Future therapies may target inflammation in the brain, improving mental health and cognitive function for those with the condition. 2. Targeted Immune Therapies to Reduce Gluten Sensitivity While a vaccine like Nexvax2 hasn’t been successful in trials, and the immune-targeting therapy larazotide acetate has also failed in trials, another promising development in celiac research is ZED1227, an experimental drug specifically designed to inhibit the body’s inflammatory response to gluten. ZED1227 works by blocking transglutaminase 2 (TG2), an enzyme that plays a critical role in the immune reaction to gluten. By targeting TG2, ZED1227 aims to prevent the immune system from attacking the gut lining when gluten is ingested, which could significantly reduce symptoms and intestinal damage for people with celiac disease. Early clinical trials have shown that ZED1227 is both safe and effective at reducing inflammation in response to gluten exposure, even in small amounts. While it’s not a cure and doesn’t replace a gluten-free diet, ZED1227 could offer a valuable safety net for individuals at risk of accidental gluten ingestion. If further trials continue to show positive results, ZED1227 could become the first medication designed to protect against gluten-induced damage, representing a major advancement in celiac disease management. 3. Enzyme Therapy as a Gluten Defense One promising area of celiac research involves enzymes designed to break down gluten before it reaches the small intestine. Scientists are investigating various enzyme therapies that could help people with celiac disease digest gluten more effectively. These enzymes, when taken as a supplement, aim to neutralize gluten before it causes damage. Although these enzymes won’t replace a gluten-free diet, they could reduce the severity of reactions after accidental gluten exposure. Enzyme therapy is currently in clinical trials, with researchers optimistic about its potential to provide a new layer of protection for those with celiac disease. 4. New Diagnostic Tests for Earlier and More Accurate Detection Diagnosing celiac disease traditionally requires a combination of blood tests and a biopsy, but researchers are exploring non-invasive alternatives. For instance, one study focused on developing a simple breath test to detect celiac-specific markers in the gut. This new method could allow for faster and less invasive screening, helping to identify celiac disease earlier in life. Early diagnosis is crucial to avoid long-term complications, such as osteoporosis and other autoimmune disorders. As these tests become more refined, they promise to simplify the diagnosis process and make it more accessible. 5. Advances in Personalized Nutrition and Microbiome Research The unique composition of each person’s gut microbiome may affect the severity of their celiac symptoms, and recent research has uncovered connections between the gut microbiome and gluten sensitivity. Scientists are studying how different bacterial strains in the gut influence immune responses to gluten. This research could lead to personalized dietary recommendations and probiotic treatments tailored to each individual’s microbiome. By adjusting gut bacteria to support digestive health, this approach may help manage symptoms more effectively and even enhance the body’s ability to tolerate small amounts of gluten. 6. CRISPR-Modified Wheat: Gene Editing for Gluten-Free Grains In a groundbreaking approach to celiac disease, scientists are exploring the use of CRISPR gene-editing technology to develop gluten-free wheat. By targeting the specific genes responsible for gluten proteins in wheat, researchers aim to “turn off” or modify the genes that trigger the immune response in people with celiac disease. Unlike traditional gluten-free options, this modified wheat would maintain the texture and nutritional profile of regular wheat, potentially providing a much-needed alternative for baking and cooking. While still in development, CRISPR-modified wheat holds great promise for those with celiac disease, offering the possibility of enjoying wheat-based products without risking an immune reaction. Early research has shown success in reducing specific gluten proteins, and with further refinement, CRISPR-modified wheat could become a viable, naturally gluten-free option. This innovation could revolutionize food choices and significantly improve quality of life for individuals with celiac disease. Looking Ahead: Hope for the Celiac Community With these advancements, the future looks brighter for those living with celiac disease. While a strict gluten-free diet remains the primary treatment, these breakthroughs represent meaningful progress in understanding and managing the disease. From vaccines and enzyme therapies to early diagnostics and microbiome research, each of these areas holds promise for improved quality of life. As research continues, the celiac community can look forward to more personalized and effective treatments, allowing for a more balanced and less restrictive lifestyle. Until then, staying informed and connected with medical updates can empower those affected by celiac disease to make educated choices about their health. Watch the video version of this article:

Celiac.com 03/07/2024 - A recent study of mice has shed light on the potential effects of chronic oral exposure to silicon dioxide (fg-SiO2), a common food additive, on food sensitivities and immune responses. This research is particularly relevant to individuals with celiac disease and other food sensitivities. Silicon dioxide, a versatile additive, plays a vital role in maintaining the quality and integrity of numerous dry and powdered food products. It can be found in ingredients of more than 2,600 processed foods worldwide, from savory soups to aromatic spices, and even infant formula. Its presence ensures that food items remain free-flowing and devoid of unsightly lumps, and it isn't always included on ingredient lists. The study, led by a team of researchers, aimed to understand how exposure to silicon dioxide, in the form of food-grade silicon dioxide (fg-SiO2), might influence the immune system's response to food antigens. Using mouse models, the researchers investigated the effects of silicon dioxide on oral tolerance (OT) induction and gluten immunopathology. The research team included Bruno Lamas, Natalia Martins Breyner,, Yann Malaisé, Mark Wulczynski, Heather J. Galipeau, Eric Gaultier, Christel Cartier, Elena F. Verdu, and Eric Houdeau. They are variously affiliated with the Toxalim (Research Centre in Food Toxicology), Team Endocrinology and Toxicology of Intestinal Barrier, INRAE/ENVT/Paul Sabatier University, Toulouse, France; and the Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Their findings revealed that exposure to silicon dioxide led to changes in immune cell function and cytokine production in the intestines. Specifically, cells from the mesenteric lymph nodes (MLNs) showed decreased proliferation and reduced secretion of key regulatory cytokines involved in OT, such as interleukin 10 (IL-10) and transforming growth factor beta (TGF-β). Furthermore, mice exposed to silicon dioxide exhibited signs of intestinal inflammation, including increased levels of fecal lipocalin-2 (Lcn-2) and interferon gamma (IFN-γ). This inflammation was associated with a breakdown of oral tolerance and alterations in immune cell populations in the intestines. Chronic Oral Exposure to Silicon Dioxide May Worsen Food Sensitivities In a mouse model of gluten-induced immunopathology, chronic exposure to silicon dioxide exacerbated intestinal damage and inflammation. These effects were observed through changes in villus-to-crypt ratio and increased infiltration of inflammatory T cells. Overall, the study suggests that chronic oral exposure to silicon dioxide may disrupt oral tolerance induction and worsen food sensitivities, particularly in individuals predisposed to conditions like celiac disease. While the study was conducted in mice, its findings underscore the need for further research to explore the potential link between silicon dioxide exposure and food sensitivities in humans. In conclusion, people with celiac disease and other food sensitivities may benefit from understanding the potential impact of food additives like silicon dioxide on their immune responses. Further investigation into this area could provide valuable insights into strategies for managing and mitigating food sensitivities in affected individuals. Read more at Environmental Health Perspectives Journal

Celiac.com 10/06/2023 - Typically, treating autoimmune diseases involves broad immunosuppression, which has various side effects. However, a team of researchers have developed a novel approach to suppress established antigen-specific immune responses without the need for global immunosuppression. The research team includes Andrew C. Tremain, Rachel P. Wallace, Kristen M. Lorentz, Thomas B. Thornley, Jennifer T. Antane, Michal R. Raczy, Joseph W. Reda, Aaron T. Alpar, Anna J. Slezak, Elyse A. Watkins, Chitavi D. Maulloo, Erica Budina, Ani Solanki, Mindy Nguyen, David J. Bischoff, Jamie L. Harrington, Rabinarayan Mishra, Gregory P. Conley, Romain Marlin, Nathalie Dereuddre-Bosquet, Anne-Sophie Gallouët, Roger LeGrand, D. Scott Wilson, Stephan Kontos, and Jeffrey A. Hubbell. They are variously affiliated with the Committee on Immunology, University of Chicago, Chicago, IL, USA; the Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA; the Committee on Cancer Biology, University of Chicago, Chicago, IL, USA; the Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; the Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France; the Animal Resources Center, University of Chicago, Chicago, IL, USA; and with Anokion US Inc., Cambridge, MA, USA. Their study introduces a new method using a polymer glycosylated with N-acetylgalactosamine (pGal) that is conjugated to the antigen. This approach enables the dissociation of the antigen upon endocytosis, allowing it to be presented in an immunoregulatory environment. The research demonstrates that pGal–antigen therapy can induce antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis, driven by the programmed cell-death-1 pathway and the co-inhibitory ligand CD276. Moreover, this therapy effectively suppresses antigen-specific responses in non-human primates vaccinated against a DNA-based simian immunodeficiency virus. In essence, pGal–antigen therapy offers a promising avenue for addressing autoimmune diseases by specifically targeting and resolving antigen-specific inflammatory T-cell responses. In the future, this approach could be applied to various autoimmune diseases, possibly even celiac disease, offering a more precise and effective alternative to current treatments that rely on broader immunosuppression. Read more in Nature Biomedical Engineering

Celiac.com 12/21/2020 - Recent leaps in understanding the development of celiac disease have led efforts toward a new, non-dietary, vaccine therapy. A lifelong gluten-free diet remains the only treatment for celiac disease, but research shows that even the most diligent gluten-free dieters are likely to be exposed to gluten on a regular basis. This is part of the appeal of safe, effective non-dietary treatments for celiac disease. And adjunctive and/or vaccine therapy is one of those approaches. New therapies might focus on immune regulation by IL-10, as in vitro models of treated celiac patients show that external IL-10 can overwhelm the gliadin driven IFN-γ response in intestinal biopsies. But, even though people with active celiac disease show high levels of anti-inflammatory IL-10 it's not enough to suppress the overwhelming Th1-mediated response. However, vaccination with gluten might trigger the extension of regulatory T cells, which could restore oral tolerance to gluten. It remains to be seen whether these approaches can strongly decrease the inflammatory intestinal response in celiac disease. A few experimental clinical trial studies have been run, though only one trial has used concurrent gliadin-based immunotherapy; that study is numbered NCT00879749 using the ClinicalTrials.gov Identifier. One recent study indicated a safety evaluation and estimates an inducible immune response by intradermal injections of Nexvax2 in treated celiac patients, which is specific to HLA-DQ2 patients. That vaccine contains three gluten peptides established by ImmunsanT for the treatment of celiac disease. These epitopes are responsible for the various immune responses by isolated T cells. A phase I in 40 HLA-DQ2+ celiac disease patients, using subcutaneous doses, showed no clinically applicable harmful effects. So far, however, few experimental therapies have been emerged as new targets for celiac disease in phase I–II trials and larger randomized controlled trials. Any suitable unique therapy needs to be harmless, operative and inexpensive. This invites further examination into the development of a new non-dietary treatment for celiac disease patients. Read the full paper by Mohammad Rostami Nejad of the Celiac Disease Department, Gastroenterology and Liver Diseases Research Center at Shahid Beheshti University of Medical Sciences in Tehran, Iran in the International Journal of Celiac Disease, 2015, Vol. 3, No. 4, 115-117.

Celiac.com 02/05/2021 - Recently, a team of doctors in the Czech Republic conducted a study of the inflammatory action of wheat gluten, and its relation to chronic diseases. Even with all of the research that has been conducted, many of the causes and mechanisms behind inflammatory and autoimmune diseases remain shrouded in mystery. Doctors just don't know what causes most autoimmune diseases or how they actually work. It is assumed that some sort of a breakdown occurs in the innate and adaptive immune system that regulates the body's mucous. On one level this makes a great deal of sense. Epithelial cells make up our skin and the linings of our respiratory, digestive and uro-genital tracts. From the moment we're born, our epithelial cells are coming into contact with the substances from the outside world. Our skin is regularly bombarded by germs, bacteria, and other foreign substances. Just the simple act of breathing brings dirt, germs, bacteria and other foreign substances into contact with the epithelial cells that line our lungs. Eating and drinking brings dirt, germs and bacteria into contact with the epithelial cells that line the digestive and uro-genital tracts. It is the job of our mucous layers, and the mucous they generate, to protect our epithelial cells that line our respiratory, digestive and uro-genital tracts. When the mucous layer fails, the immune system can be stressed. When the immune system breaks down or over-reacts, autoimmune ailments can result. Unlike the multiple layers of epithelial cells that form the protective layers of our skin, just a single layer of epithelial cells protects our uro-genital, respiratory and digestive tracts. Many people are surprised to learn that the surface area of human skin averages just two square meters in size, while of the lining of the respiratory, digestive and uro-genital tracts average about 300 square meters. Again, these surfaces are mostly covered with just a single layer of epithelial cells, yet to fend off the millions of micro-organisms that regularly bombard them they must be able to tell the bad from the good microorganisms and to keep the bad ones from crossing the epithelial barrier. Unlike other food proteins, the group of proteins in wheat, known as gliadin, has the ability to cause immune cells to produce cytokines. Cytokines are proteins and peptides that function as signaling compounds. Simply put, they tell other cells what to do. Inflammatory Activity of Gluten in Chronic Disease In the case of celiac disease, the presence of wheat protein activates immune cells to produce cytokines that tell the cells lining the intestine to become inflamed as a means of protecting the body against what it sees as a foreign invader. In the skin, mucosa, and lymphoid tissues there is a highly specialized kind of white blood cell called a dendritic cell. The role of dendritic cells is to initiate a primary immune response by activating lymphocytes and secreting cytokines. Research has shown that when these dendritic cells are exposed to wheat gliadin, they cause the body to increase the production of cytokines, which in turn triggers inflammation of the mucosal layer. This pattern of activity seems to play an important part in celiac disease. As stated earlier, this thin epithelial layer is all that protects the body from invasion by harmful intruders. It is also a place where nutrient exchange occurs. In the respiratory tract, oxygen is exchanged. In the digestive tract, nutrients are absorbed. In fact, for nutrients to be absorbed, it is necessary for there to be a degree of permeability in these cell linings. If they kept everything out, we'd die of malnutrition, or maybe thirst. If they let everything in, we'd likely die of one disease or another. So, the body keeps up a delicate balancing act here. In fact, the body has developed a highly sophisticated system of mechanical and chemical mechanisms whose job it is to protect this single layer of epithelial cells by identifying, degrading and removing intruders, while identifying and permitting beneficial items like nutrients to pass freely into the body for processing. In healthy folks, this process works very smoothly. The bad stuff is broken down and cleaned out, while the good stuff is permitted to cross the barrier and to carry the proper nutrients to our bodies. Once we leave the sterile environment of the womb, billions of different bacteria begin to colonize most of our mucosal and skin surfaces. Whether a person is healthy or not, the number of foreign bacterial cells living on and in our bodies far outnumber the cells we have when we are born. Most of these bacteria are beneficial, with the most beneficial bacteria residing in the gut. In fact, there are so many different kinds, with such high levels of specificity, that scientists haven't yet been able to cultivate all of them. These beneficial bacteria in the gut play an important role in immunity, metabolism, and other activities. Gluten's Connection to Various Chronic Diseases A wide range of inflammatory and autoimmune diseases are associated with celiac disease and untreated celiac patients, including a higher risk of complications from anemia, infertility, osteoporosis, and gastrointestinal cancer. Many other disorders are associated with celiac disease, including endocrine diseases like type 1 diabetes, thyroiditis, connective tissue diseases, liver diseases, and Down syndrome, along with nervous system disorders like epilepsy, ataxia, and peripheral neuropathy. One of the strongest associations with celiac disease is autoimmune diabetes. We now know that 5-10% of diabetic patients have celiac disease, a rate more than 5 to 10 times that of the general population. Almost all of these patients improve on a gluten-free diet. It's unclear why a gluten-free diet might produce improvement in some of these people with these conditions, but one prominent hypothesis is that a percentage of folks with those conditions have compromised gut barriers that somehow permit undigested gluten that provokes an immune response. An interesting side-note here is that mainstream researchers have recently begun to admit that diabetes, which was previously thought to be "exclusively" endocrine in nature, and heart disease, which was thought to be "purely" circulatory in nature, are both characterized by an inflammation component. In other words, inflammation of tissue, and therefore, of cells, plays an important part in both diseases. Similarly, celiac disease, which was thought to be largely gastrointestinal in nature, is increasingly showing connections to a wide range of disorders that affect nearly every major organ in the body. Strangely, or perhaps not so strangely in light of this recent evidence, a gluten-free diet seems to have a beneficial effect on a number of chronic diseases in people who are entirely free of celiac disease. Some patients with psoriasis and urticaria, for example, have shown improvement with a gluten-free diet, as have some patients with cryptogenic ataxia and peripheral neuropathy. A number of schizophrenics have shown a reduction of symptoms on a gluten-free diet. Also, a number of people with rheumatoid arthritis who observe a vegan, gluten-free diet have reported improvement in their condition. Animal models have proven to be helpful in better understanding many different diseases and to help create new and more effective treatments. There's a whole specialized area of biology called "Gnotobiology." These people specialize in working in germ-free conditions. Gnotobiologists have developed strains of animals that are reared in germ-free environments. Imagine if you had never been exposed to any of the harmful or beneficial bacteria that colonize the human body once it leaves the sterile environment of the womb. You would make a great guinea pig for better understanding how disease might work. Like people, once rats are born, they undergo a profound change. Intestinal microflora have a major effect on their mucosal immune system. One of the benefits of using gnotobiotic animal models is that researchers can separate the effects of microflora and dietary antigens. Since scientists know that applying wheat-gliadin to the gastro-intestinal tracts of conventionally raised rats of the AVN strain beginning shortly after birth results in pronounced jejunal changes, that is, celiac-associated lesions, it's beneficial if they can have a "clean" group of rats to test and compare against the conventionally raised rat group to see if there's some kinds of microflora that might provide some protection against celiac disease. One of the things that the research team discovered is that breastfeeding seemed to be profoundly protective against the adverse effects of wheat gluten. The research team actually looked at rat pups in which they had induced enteropathy to compare those given breast milk to those handfed on formula. Among other things, they found that rats that were suckled never showed flat mucosa so characteristic of celiac damage when exposed to wheat-gliadin. Its unclear exactly why this is, though breast milk has so many beneficial elements to it, that it's hard to imagine it not being responsible for a great deal of immune-related development in general. Rat breast milk in particular imparts epidermal growth factor (EGF), which seems to play an important part in of the rat's jejunal cells. The research team also studied the effects of gliadin in a model system. In fact, the team was able to take a close look at the effects of gluten on cells within the stomach cavities of mice. In one test, a group of rats received epidermal growth factor via breast milk, while another group received straight formula with no EGF. Both were treated with wheat-gliadin. Rats without EGF showed villous atrophy, while those receiving breast milk, and thus, EGF, were protected against pathological mucosal changes and also against celiac-associated damage. Basically, it all boils down to several things: First, it looks very much like the way is paved for the development of celiac disease by the innate immune system when the presence of gliadin promotes functional and phenotypic maturing in dendritic white blood cells, which then leads to the gliadin peptides being presented to certain T lymphocytes, which then trigger the associated inflammation and resulting damage. The research team concluded that it does, indeed, seem to be the unique structure of gluten and its fragments that provokes the response from the mechanisms of innate immunity. In predisposed individuals, gluten seems to more readily activate an immune response than other proteins like soy protein and egg protein. Breastfeeding seems to offer some protection against gluten intolerance and associated damage. In many cases, a gluten-free diet brings about improvement in chronic inflammatory and autoimmune diseases. Celiac disease is just one of many inflammatory and autoimmune diseases to be associated with the intestinal damage arising from chronic exposure to gluten in gluten-intolerant individuals. Also, many inflammatory and autoimmune diseases show improvement once gluten is excluded from the diet. Reference: Published In "Inflammation and Infection. The Golden Triangle: Food—Microflora—Host Defense". P.J. Heidt, Z. Midtvedt., V. Rusch, D. van der Waaij (Eds.) Old Herborn University Seminar Monography, 2007

Celiac.com 12/31/2012 - In people with celiac disease, eating wheat, barley, or rye triggers inflammation in the small intestine. Left unchecked, this inflammation causes the gut damage that is associated with untreated celiac disease. Specifically, the storage proteins in these grains (gluten) trigger an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. Researchers actually have a pretty good understanding of this aspect of celiac disease, part of a process called adaptive immunity. However, there has been some research that suggests that gluten proteins might trigger an immune response in people who do not have celiac disease, and who do not carry the HLA-DQ2 or HLA-DQ8 genetic markers that predispose them to developing celiac disease. Such a response is part of a process called innate immunity, and is far less understood than the adaptive immunity process. The innate immune system provides an early response to many microbial and chemical stimuli and is critical for successful priming of adaptive immunity. To better understand the relationship between adaptive immunity and innate immunity in celiac disease, a research team recently set out to determine if gliadin digests might induce innate immune responses in celiac and non-celiac individuals. Specifically, they wanted to know if wheat amylase trypsin inhibitors drive intestinal inflammation, and if so, by what receptor mechanism. The research team included Yvonne Junker, Sebastian Zeissig, Seong-Jun Kim, Donatella Barisani, Herbert Wieser, Daniel A. Leffler, Victor Zevallos, Towia A. Libermann, Simon Dillon, Tobias L. Freitag, Ciaran P. Kelly, and Detlef Schuppan. They are affiliated variously with the Division of Gastroenterology and the Proteomics and Genomics Center at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, with the Department of General Pediatrics and the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein Kiel in Kiel, Germany, the Department of Experimental Medicine at the University of Milano-Bicocca in Milan, Italy, the German Research Center for Food Chemistry in Garching, Germany, the Hans-Dieter-Belitz-Institute for Cereal Grain Research in Freising, Germany, the Division of Molecular and Translational Medicine in the Department of Medicine I at Johannes Gutenberg University in Mainz, Germany, and with the Department of Bacteriology and Immunology at the Haartman Institute at the University of Helsinki in Finland. A number of earlier studies (Molberg et al., 1998; Anderson et al., 2000; Shan et al., 2002) have found HLA-DQ2– and HLA-DQ8–restricted gluten peptides that trigger the adaptive immune response in people with celiac disease. However, only 2–5% of individuals who show these HLAs develop celiac disease, which means that other factors, especially innate immune activation, are at play in the generation of celiac disease. Responsive innate cells are primarily macrophages, monocytes, DCs, and polymorphonuclear leukocytes that by means of their pattern-recognition receptors, such as TLRs, trigger the release of proinflammatory cytokines and chemokines, resulting in recruitment and activation of additional inflammatory cells (Medzhitov, 2007). Earlier studies (Maiuri et al., 2003) showed that peptides p31-43 or p31-49 from α-gliadin, that lack adaptive stimulatory capacity, triggered innate immune reactions by inducing IL-15 and Cox-2 expression in patient biopsies, and MHC class I polypeptide–related sequence A (MICA) on intestinal epithelial cells (Hüe et al., 2004). However, these studies have proven difficult to reproduce in cell culture, and researchers could not identify any specific receptor responsible for the observed effects. In a subsequent study, gliadin, in cell culture, reportedly triggered increased expression of co-stimulatory molecules and the production of proinflammatory cytokines in monocytes and DCs (Nikulina et al., 2004; Cinova et al., 2007). Two other studies (Thomas et al., 2006; Lammers et al., 2008) implicated the chemokine receptor CXCR3 in increased intestinal epithelial permeability upon gliadin challenge in a MyD88-dependent manner. However, those studies failed to reproducibly identify a specific gliadin peptide as the trigger. So far, no clear picture of the role of the innate immune system in celiac disease has emerged. In this study, the researchers show that members of the non-gluten α-amylase/trypsin inhibitors (ATIs), CM3 and 0.19, pest resistance molecules in wheat and related cereals, are strong triggers of innate immune responses in human and murine macrophages, monocytes, and dendritic cells. Their results show that ATIs activate the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients’ biopsies. They also show that mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders. The findings of this study mean that the proteins in wheat may trigger immune reactions not just in people with celiac disease, but in people without celiac disease, and that these reactions may be actively contributing to the development of numerous other intestinal and non-intestinal immune disorders. That's a pretty big deal. Stay tuned to see how future studies elaborate these findings. Read the entire study in the Journal of Experimental Medicine. Source: J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660

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: Open Original Shared Link

Celiac.com 08/13/2012 - Research has indicated that giving small amounts of wheat-rich food to people with celiac disease, who are on a gluten-free diet, will trigger interferon (IFN)-γ-secreting T cells in the bloodstream. These T cells react to gluten, and can be easily detected. However, very little is known about how this procedure might be reproduced in the same patient groups that underwent two, or more, gluten challenges. A team of researchers recently set out to assess the reproducability of this short wheat challenge method for detecting immune an response to gluten. The research team included A. Camarca, G. Radano, R. Di Mase, G. Terrone, F. Maurano, S. Auricchio, R. Troncone, L. Greco, C. Gianfrani. They are affiliated with the Institute of Food Sciences-CNR, Avellino Department of Paediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University of Naples, Naples, Italy. They evaluated fourteen celiac patients in remission who consumed wheat bread for 3 days, along with thirteen patients who underwent a second gluten challenge after 3-10 months on a strict gluten-free diet. The team then analyzed the immune reactivity to gluten in peripheral blood by detecting IFN-γ both before and 6 days after patients began a a gluten-inclusive diet. They found that gliadin-specific IFN-γ-secreting CD4(+) T cells increased significantly by day 6 of the first challenge. These cells arose as prevalently human leucocyte antigen (HLA)-DQ restricted and with a phenotype of gut homing, as suggested by the expression of β7-integrin. They also saw a reaction to gliadin after the second wheat consumption, although the responses varied by individual at each challenge. The study showed that a short wheat challenge offers a non-invasive approach to investigate the gluten-related immune response in peripheral blood of people who are sensitive to gluten. Moreover, the study showed that the procedure can be reproduced in the same subjects after a gluten wash-out of at least 3 months. The results of this study mean that we can likely expect this procedure to find its way into clinical practice in the future. Source: Clinical and Experimental Immunology. 2012 Aug;169(2):129-36. doi: 10.1111/j.1365-2249.2012.04597.x.

Celiac.com 09/13/2010 - What's happening in with the immune system when a child is first diagnosed with celiac disease? What happens when they are treated with a gluten-free diet? Some recent studies have indicated that both the adaptive and the innate immune system play roles in celiac disease. However, until now, doctors haven't known much about the immune phenotype of children with celiac disease and how that phenotype might by affected by a gluten-free diet. To move toward a better understanding of these issues, a team of researchers recently studied immune phenotype in children with either newly diagnosed celiac disease, or celiac disease treated with a gluten-free diet. The research team included Áron Cseh, Barna Vásárhelyi, Balázs Szalay, Kriszta Molnár, Dorottya Nagy-Szakál, András Treszl, Ádám Vannay, András Arató, Tivadar Tulassay and Gábor Veres. The are affiliated with the First Department of Pediatrics in the Research Group for Pediatrics and Nephrology at Semmelweis University and Hungarian Academy of Sciences, in Budapest, Hungary. For their study, the team described the status of major players within the adaptive and innate immune system in peripheral blood of children with newly diagnosed celiac disease. They then looked to see how the phenotype might have changed once the symptoms improved following treatment with a gluten-free diet. The team drew peripheral blood samples from ten children with biopsy-proven celiac disease at the time of diagnosis and again after once clinical symptoms subsided with treatment by gluten-free diet. They also drew blood samples from a control group of 15 children who suffered from functional abdominal pain. They measured the prevalence of cells of adaptive and innate immunity by means of labeled antibodies against surface markers and intracellular FoxP3 using a flow cytometer. They found that patients with celiac disease had lower T helper, Th1 and natural killer (NK), NKT and invariant NKT cell prevalence and with higher prevalence of activated CD4+ cells, myeloid dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and monocytes compared to controls. Most of these deviations returned to normal, once symptoms subsided with gluten-free diet treatment. However, prevalence of NK and NKT cell, DC and TLR-2 expressing DCs and monocytes remained abnormal. The immune phenotype in childhood celiac disease indicates that both adaptive and innate immune systems are playing a role in celiac disease. Treatment with a gluten-free diet reverses immune abnormalities, but the mechanics of the reversal likely varies among cell types. Source: Dig Dis Sci. 2010 Aug 5. DOI: 10.1007/s10620-010-1363-6