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    • Scott Adams

      Frequently Asked Questions About Celiac Disease   04/24/2018

      This Celiac.com FAQ on celiac disease will guide you to all of the basic information you will need to know about the disease, its diagnosis, testing methods, a gluten-free diet, etc.   Subscribe to Celiac.com's FREE weekly eNewsletter   What is Celiac Disease and the Gluten-Free Diet? What are the major symptoms of celiac disease? Celiac Disease Symptoms What testing is available for celiac disease?  Celiac Disease Screening Interpretation of Celiac Disease Blood Test Results Can I be tested even though I am eating gluten free? How long must gluten be taken for the serological tests to be meaningful? The Gluten-Free Diet 101 - A Beginner's Guide to Going Gluten-Free Is celiac inherited? Should my children be tested? Ten Facts About Celiac Disease Genetic Testing Is there a link between celiac and other autoimmune diseases? Celiac Disease Research: Associated Diseases and Disorders Is there a list of gluten foods to avoid? Unsafe Gluten-Free Food List (Unsafe Ingredients) Is there a list of gluten free foods? Safe Gluten-Free Food List (Safe Ingredients) Gluten-Free Alcoholic Beverages Distilled Spirits (Grain Alcohols) and Vinegar: Are they Gluten-Free? Where does gluten hide? Additional Things to Beware of to Maintain a 100% Gluten-Free Diet What if my doctor won't listen to me? An Open Letter to Skeptical Health Care Practitioners Gluten-Free recipes: Gluten-Free Recipes
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    Suppressive Function of Regulatory T Cells Impaired in Celiac Patients


    Jefferson Adams


    • Does Treg cell dysfunction play a major role in celiac disease pathogenesis?


    Celiac.com 06/21/2017 - Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease. What does that mean?


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    Although researchers understand the effector T-cell response in patients with celiac disease pretty well, they really don't know very much about the role played by regulatory T cells (Treg cells) in the loss of tolerance to gluten. To get a better picture, a team of researchers recently set out to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells.

    The research team included L Cook, CML Munier, N3 Seddiki, D van Bockel, N Ontiveros, MY Hardy, JK Gillies, MK Levings, HH Reid, J Petersen, J Rossjohn, RP Anderson, JJ Zaunders, JA Tye-Din, AD Kelleher.

    For the study, gluten-free patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. The research team collected peripheral blood before and after challenge. To effectively measure the gluten-specific CD4+ T-cell response, they combined traditional IFN-γ ELISpot with a test for antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation, but relies instead on antigen-induced co-expression of CD25 and OX40 (CD134).

    During the gluten challenge, levels of circulating gluten-specific Treg cells and effector T cells both rose sharply, peaking on the sixth day.

    The team recounts surprise on discovering that about 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Even though they saw normal suppressive function in peripheral polyclonal Treg cells from celiac patients, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells showed sharply reduced suppressive function compared with polyclonal Treg cells.

    The team's study offers the first estimates of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of celiac patients.

    FOXP3+CD39+ Treg cells made up the majority of all circulating gluten-specific CD4+ T cells, but they showed reduced suppressive function, indicating that Treg cell dysfunction might be a key factor in celiac disease development.

    This type of research is crucial to help document the genetic physiology of celiac disease, which will help researchers to better understand and treat the disease itself.

    Source:

    • J Allergy Clin Immunol. 2017 Mar 8. pii: S0091-6749(17)30343-3. doi: 10.1016/j.jaci.2017.02.015.

       

      The researchers are variously affiliated with the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia, St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia; the Infection and Immunity Program, The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia; the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia; St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia, Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; the Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom; the Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; ImmusanT, Cambridge, Massachusetts; and the Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Australia.


    Image Caption: Is Treg cell dysfunction a key factor in celiac disease development? Photo: Zappys Technology Solutions
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  • Related Articles

    Jefferson Adams
    Celiac.com 04/28/2016 - The development of celiac disease has been tied to polymorphisms in the regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but existing data are unclear and contradictory.
    A research team recently set out to examine the associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and rs17810546 in IL12A) with celiac disease risk using meta-analysis.
    The research team included Cong-Cong Guo, Man Wang, Feng-Di Cao, Wei-Huang Huang, Di Xiao, Xing-Guang Ye, Mei-Ling Ou, Na Zhang, Bao-Huan Zhang, Yang Liu, Guang Yang, and Chun-Xia Jing.

    They are variously affiliate with the Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, the Department of Stomatology of the First Affiliated Hospital of Jinan University, Guangzhou, the Department of Parasitology, School of Medicine, Jinan University, Guangzhou, and the Key Laboratory of Environmental Exposure and Health in Guangzhou, Jinan University, Guangzhou, China.
    The team began by searching PubMed and Web of Science for RGS1 rs2816316 and IL12A rs17810546 with celiac disease risk. They then estimated the odds ratio (OR) and 95% confidence interval (CI) of each SNP. They retrieved a total of seven studies, and used Stata 12.0 to perform statistical analyses.
    The available data indicated the minor allele C of rs2816316 was negatively associated with celiac disease (C vs. A: OR = 0.77, 95% CI = 0.74–0.80), while they did find a positive association for the minor allele G of rs17810546 (G vs. A: OR = 1.37, 95% CI = 1.31–1.43).
    They found that the co-dominant model of genotype effect confirmed the significant associations between RGS1 rs2816316/IL12A rs17810546 and celiac disease. They found no evidence of any publication bias.
    The team's meta-analysis indicates a connection between RGS1 and IL12A and celiac disease, and provides a strong support for deeper study into the roles of RGS1 and IL12A in the development of celiac disease.
    Source:
    Int. J. Mol. Sci. 2016, 17(4), 457; doi:10.3390/ijms17040457

    Jefferson Adams
    Celiac.com 05/30/2016 - People with HLA genes have the highest risk factor for developing autoimmune disorders. The vast majority of people with celiac disease carry the HLA DQA1*05 and DQB1*02 alleles, both of which encode the DQ2.5 molecule.
    A research team recently set out to examine the implications for anti-gluten T cell response of the preferential expression of HLA-DQ2.5 genes associated with celiac disease with respect to non-predisposing HLA genes. The research team included L Pisapia, A Camarca, S Picascia, V Bassi, P Barba, G Del Pozzo, and C Gianfrani. They are variously affiliated with the Institute of Protein Biochemistry-CNR, the Institute of Genetics and Biophysics-CNR in Naples, Italy, and the Institute of Food Sciences-CNR in Avellino, Italy.
    In order to activate pathogenic CD4+ T lymphocytes, that is, to trigger active celiac disease, it is necessary for the body to form complexes between DQ2.5 and gluten peptides on antigen-presenting cells (APCs). It is widely accepted by clinicians that the DQ2.5 genes establish the different intensities of anti-gluten immunity, depending on whether they are in a heterozygous or a homozygous configuration, that is, whether both genes are activated, or only one gene is activated.
    The research team's recent study shows that, in celiac patients, HLA DQA1*05 and DQB1*02 gene expression is much higher than expression of non-celiac-associated genes. This, in turn, impacts protein levels and causes a comparable cell surface exposure of DQ2.5 heterodimers between DQ2.5 homozygous and heterozygous celiac patients. As a consequence, the magnitude of the anti-gluten CD4+ T cell response is strictly dependent on the antigen dose, and not on the DQ2.5 gene configuration of APCs.
    These findings are important, because they support the idea that the expression of DQ2.5 genes is an important risk factor in celiac disease.
    The preferential expression of DQ2.5 alleles observed in this study offers a new explanation of why these genes are so frequently associated with celiac disease and with other autoimmune disorders.
    Source:
    J Autoimmun. 2016 Apr 12. pii: S0896-8411(16)30029-4. doi: 10.1016/j.jaut.2016.03.016.

    Jefferson Adams
    Celiac.com 08/09/2016 - Some researchers have suggested that gluten may not be the actual trigger of symptoms in non-celiac gluten sensitivity. Others feel that gluten is definitely the trigger, especially in certain cases.
    A team of researchers recently set out to evaluate patients with clinical non-celiac gluten sensitivity (NCGS), who presented with lymphocytic enteritis, positive celiac genetics and negative celiac blood tests. The team felt that the results would confirm that gluten is, in fact, the trigger of symptoms in this subgroup of patients.
    The research team included M Rosinach, F Fernández-Bañares, A Carrasco, M Ibarra, R Temiño, A Salas, and M Esteve. They are variously affiliated with the Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain, and with the Department of Pathology, Hospital Universitari Mutua Terrassa, Terrassa in Barcelona, Spain.
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    Eleven of the patients received 20 grams per day of gluten, while the seven others received a non-gluten placebo. The team measured clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits.
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    This study shows that gluten is definitely the trigger for symptoms in a subgroup of patients with clinical NCGS. After a gluten-free diet patients experienced positive celiac genetics, lymphocytic enteritis, and clinical and histological remission.
    Source:
    PLoS One. 2016 Jul 8;11(7):e0157879. doi: 10.1371/journal.pone.0157879. eCollection 2016.

    Jefferson Adams
    Celiac.com 05/18/2017 - Researchers understand pretty well that celiac disease is driven in part by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides.
    Mast cells are innate immune cells that produce a majority of co-stimulatory signals and inflammatory mediators in the intestinal mucosa. A team of researchers recently set out to evaluate the role of mast cells in the development of celiac disease.
    The research team included Barbara Frossi, PhD, Claudio Tripodo, MD, Carla Guarnotta, PhD, Antonio Carroccio, MD, Marco De Carli, MD, Stefano De Carli, MD, Marco Marino, MD, Antonino Calabrò, MD, and Carlo E. Pucillo, MD.
    They are variously affiliated with the Department of Gastroenterology and Digestive Endoscopy at the University Hospital of Udine in Udine, Italy; the Department of Medical and Biological Sciences, University of Udine, Udine, Italy; the Second Unit of Internal Medicine, University of Udine, Udine, Italy; the Department of Experimental and Clinical Biomedical Sciences “Mario Serio,” University Hospital of Florence, Florence, Italy; the Tuscany Referral Center for Adult Coeliac Disease, AOU Careggi, Florence, Italy; the Department of Health Science, University Hospital of Palermo in Palermo, Italy; and the Department of Internal Medicine and Specialist at the University Hospital of Palermo in Palermo, Italy.
    For their study, the research team scored intestinal biopsy results from celiac patients according to Marsh classification, and characterized those results for leukocyte infiltration and MC distribution. They also characterized mast cell reactivity to gliadin and its peptides via in vitro assays.
    The team found that infiltrating mast cells reflected the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. They noted that mast cells responded directly to non-immunodominant gliadin fragments by releasing pro-inflammatory mediators.
    Their immunohistochemical analysis of infiltrating mast cells, along with the effects of gliadin peptides on intestinal mast cells, indicates that patients in with advanced celiac disease face an increase in pro-inflammatory mast cell function. This result was also tied to increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage.
    This study clearly describes the progressive stages of celiac disease, and shows that mast cells are a prominent feature of the inflammatory process.
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     Source:
    Journal of Allergy, & Clinical Immunology. DOI: http://dx.doi.org/10.1016/j.jaci.2016.08.011

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    Jefferson Adams
    Celiac.com 05/22/2018 - Proteins are the building blocks of life. If scientists can figure out how to create and grow new proteins, they can create new treatments and cures to a multitude of medical, biological and even environmental conditions.
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    Source:
    Bloomberg.com

    Jefferson Adams
    Celiac.com 05/21/2018 - Just a year ago, Starbucks debuted their Canadian bacon, egg and cheddar cheese gluten-free sandwich. During that year, the company basked in praise from customers with celiac disease and gluten-sensitivity for their commitment to delivering a safe gluten-free alternative to it’s standard breakfast offerings.
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    Jefferson Adams
    Celiac.com 05/19/2018 - Looking for a nutritious, delicious meal that is both satisfying and gluten-free? This tasty quinoa salad is just the thing for you. Easy to make and easy to transport to work. This salad of quinoa and vegetables gets a rich depth from chicken broth, and a delicious tang from red wine vinegar. Just pop it in a container, seal and take it to work or school. Make the quinoa a day or two ahead as needed. Add or subtract veggies as you like.
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    Jefferson Adams
    Celiac.com 05/18/2018 - Across the country, colleges and universities are rethinking the way they provide food services for students with food allergies and food intolerance. In some cases, that means major renovations. In other cases, it means creating completely new dining and food halls. To document both their commitment and execution of gluten-free and allergen-free dining, these new food halls are frequently turning to auditing and accreditation firms, such as Kitchens with Confidence.
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    Zyana Morris
    Celiac.com 05/17/2018 - Celiac disease is not one of the most deadly diseases out there, but it can put you through a lot of misery. Also known as coeliac, celiac disease is an inherited immune disorder. What happens is that your body’s immune system overreacts to gluten and damages the small intestine. People who suffer from the disease cannot digest gluten, a protein found in grain such as rye, barley, and wheat. 
    While it may not sound like a severe complication at first, coeliac can be unpleasant to deal with. What’s worse is it would lower your body’s capacity to absorb minerals and vitamins. Naturally, the condition would cause nutritional deficiencies. The key problem that diagnosing celiac is difficult and takes take longer than usual. Surprisingly, the condition has over 200 identified symptoms.
    More than three million people suffer from the coeliac disease in the United States alone. Even though diagnosis is complicated, there are symptoms that can help you identify the condition during the early stages to minimize the damage. 
    Here is how you can recognize the main symptoms of celiac disease:
    Diarrhea
    In various studies conducted over years, the most prominent symptom of celiac disease is chronic diarrhea.
    People suffering from the condition would experience loose watery stools that can last for up to four weeks after they stop taking gluten. Diarrhea can also be a symptom of food poisoning and other conditions, which is why it makes it difficult to diagnose coeliac. In certain cases, celiac disease can take up to four years to establish a sound diagnosis.
    Vomiting
    Another prominent symptom is vomiting.  
    When accompanied by diarrhea, vomiting can be a painful experience that would leave you exhausted. It also results in malnutrition and the patient experiences weight loss (not in a good way though). If you experience uncontrolled vomiting, report the matter to a physician to manage the condition.
    Bloating
    Since coeliac disease damages the small intestine, bloating is another common system. This is due to inflammation of the digestive tract. In a study with more than a 1,000 participants, almost 73% of the people reported bloating after ingesting gluten. 
    Bloating can be managed by eliminating gluten from the diet which is why a gluten-free diet is necessary for people suffering from celiac disease.
    Fatigue
    Constant feeling of tiredness and low energy levels is another common symptom associated with celiac disease. If you experience a lack of energy after in taking gluten, then you need to consult a physician to diagnose the condition. Now fatigue can also result from inefficient thyroid function, infections, and depression (a symptom of the coeliac disease). However, almost 51% of celiac patients suffer from fatigue in a study.
    Itchy Rash
    Now the chances of getting a rash after eating gluten are slim, but the symptom has been associated with celiac disease in the past. The condition can cause dermatitis herpetiformis, which causes a blistering skin rash that occurs around the buttocks, knees, and elbows. 
    A study found out that almost 17% of patients suffering from celiac disease might develop dermatitis herpetiformis due to lack of right treatment. Make sure you schedule an online appointment with your dermatologist or visit the nearest healthcare facility to prevent worsening of symptoms.
    Even with such common symptoms, diagnosing the condition is imperative for a quick recovery and to mitigate the long-term risks associated with celiac disease. 
    Sources:
    ncbi.nlm.nih.gov  Celiac.com ncbi.nlm.nih.gov  mendfamily.com