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Celiac.com 05/04/2020 - The demise of the Nexvax2 vaccine for celiac disease, coupled with more research that shows regular gluten ingestion for most people with celiac disease, points to a more prominent roll for enzymes, but absent a vaccine, what does a perfect world look like for people with celiac disease? Easy home celiac testing, regular gluten monitoring, and gluten-busting enzymes are three things that people with celiac disease would have in a perfect world. Regular Gluten Exposure for Most Gluten-Free Celiacs If you have celiac disease, you’re probably eating gluten more frequently than you realize, whether or not you have symptoms. Whether they know it or not, the vast majority of celiacs are eating gluten on a regular basis. In fact, one recent study showed that up to 90% people with celiac disease are being exposed to gluten when they eat outside their homes. Celiac and Gluten Testing In a perfect world, people who suspected celiac disease would be able to do an easy, reliable test at home to determine if they had celiac disease, or if they needed further screened and assessment by a doctor. They would also be able to test regularly to see if they are getting exposed to gluten in their otherwise gluten-free diet. We've written about when to use home celiac test kits. We've reviewed the LetsGetChecked Home Celiac Disease Test Kit Home celiac test kits are a popular topic on our celiac and gluten-free forum. Gluten Monitoring in Celiac Patients In a perfect word, people with celiac disease would be regularly monitored for gluten levels, much like diabetics are monitored for glucose levels. Currently, there are no home kits that monitor gluten without the user sending samples to a lab. However, there are a few good home test kits that use clinical labs to deliver accurate results fairly quickly. These tests are great for monitoring general gluten levels to spot check your diet. Home Gluten Test Kits Finger Prick Blood Test for Gluten Microdrop Health, a Houston-based company today began offering its imaware™ celiac disease test to patients for monitoring, through use of anti-tissue transglutaminase (tTG) and deaminated gliadin peptide (DGP) blood test results. Home Stool & Urine Testing for Gluten Stool and urine testing is slowly moving mainstream. Gluten Detective claims to offer the only home test for gluten exposure. They also claim that stool testing can detect celiac disease before gut damage occurs, in many cases. Enzymes to Break Down Gluten For individual consumption - Oral are enzymes are enzymes that you take by mouth and which break down gluten. For oral enzymes to protect people with celiac disease, the enzymes need to break down the gluten proteins in the stomach, before they get to the small intestine, where they cause the gut damage typical of untreated celiac disease. That can be tricky for many reasons, including the amount of gluten consumes, individual gluten sensitivity levels, and level of gut healing, etc. AN PEP is one enzyme currently proven to break down gluten in the stomach before it gets to the gut, but it's only intended to protect against incidental gluten ingestion, and not meant to make gluten safe for people with celiac disease. Currently, there are no oral enzymes on the market that can make gluten safe for people with celiac disease to consume. All enzymes, including AN PEP, are intended solely for episodes of minor and occasional gluten ingestion. Still, regular or strategic use of an oral AN PEP enzyme could provide some protection against the gluten ingestion that seems to be so common with celiacs. The anecdotal evidence is convincing, and stories like the one that found its way into a review of a particular brand of AN PEP formula, called GliadinX, are not uncommon. Dry Enzymes For Manufacturing - Dry enzymes are enzymes that could be added to traditional gluten ingredients, such as flour, in bulk manufacturing, to break down the gluten and render the products safe for people with celiac disease. In a perfect world, food manufacturers could add a dry, temperature stable gluten-busting enzyme to traditional wheat ingredients to render foods safely gluten-free, or gluten-removed. Dry glutenase enzymes would work much the same way lactase works to make milk lactose free and safe for most people with milk intolerance. A team of researchers at Clemson University is currently pursuing a project to make dry enzymes heat stable for breaking down gluten in manufactured foods to create safe, gluten-removed foods for people with celiac disease or gluten sensitivity. Why Digesting Gluten is Better than Dissolving Gluten We see numerous comments in our forums where people seem to refer to the concept of "dissolving" gluten, instead of digesting or breaking down gluten. In healthy digestion, gluten gets broken down into tiny particles that the body can handle, without causing inflammation or adverse immune reactions. That's what most people mean when the refer to 'dissolving' gluten. Simply dissolving gluten wouldn't help people with celiac disease, because merely dissolving gluten wouldn't render it safely digestible. So, enzymes work by breaking down gluten gluten, not by dissolving gluten. The distinction is important. In a perfect world people with celiac disease would have access to easy, reliable home testing and gluten monitoring. They would also have access to effective enzymes to help prevent damage from the gluten exposure that is common in celiacs, even among those on a gluten-free diet.
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Celiac.com 12/04/2019 - There still is no easy and accurate way to monitor and diagnose celiac disease in patients who've been on a gluten-free diet for a while. Celiac disease patients on a gluten-free diet experience reactions to gluten, but researchers really don't understanding those reactions in any meaningful way. Systemic cytokine release was recently linked to reactivation of gluten immunity in celiac disease. A team of researchers recently set out to define the nature and time-course of symptoms and interleukin-2 changes specific for celiac disease patients. Their study shows that interleukin-2 assessment could help doctors monitor and diagnose celiac disease in patients already following a gluten-free diet. The research team included Jason A. Tye-Din, A. James M. Daveson, Hooi C. E, Gautam Goel, James MacDougall, Sarah Acaster, Kaela E. Goldstein, John L. Dzuris, Kristin M. Neff, Kenneth E. Truitt and Robert P. Anderson. They are variously affiliated with the Immunology Division, Department of Medical Biology, The Walter and Eliza Hall Institute, University of Melbourne, Parkville, Vic., Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Vic., Australia; University of Queensland, Brisbane, Qld, Australia; Sir Charles Gairdner Hospital, Perth, WA, Australia; ImmusanT, Inc., Cambridge, MA, USA; Prometrika, LLC, Cambridge, MA, USA; and Acaster Lloyd Consulting Ltd., London, UK. The team presented a gluten challenge to 25 celiac disease patients following a gluten-free diet, and to 25 healthy control subjects. Each group consumed a standardized 6 gram gluten challenge. The team compiled a Celiac Disease Patient-Reported Outcome survey and global digestive symptom assessment each hour for up to 6 hours after gluten challenge. They also recorded adverse events over a 48 hour period, and assessed serum interleukin-2 levels at baseline, and at 2, 4 and 6 hours. Healthy control subjects showed no detectable levels of serum interleukin-2, while 92% of celiac patients showed no detectable levels at baseline, but levels >0.5 pg/ml at 4 hours. Patient-reported outcome severity scores remained steady for all control subjects, while scores for celiac patients rose sharply after gluten in celiac disease patients. Symptoms of gluten exposure started at the 1 hour mark, and topped out after three hours. Patients with serious reactions typically suffered from nausea and vomiting, while those with milder reactions experienced headache and fatigue. The highest interleukin-2 levels were associated with more severe symptoms, especially nausea and vomiting. The timing and severity of gluten ingestion symptoms in people with celiac disease are strongly connected to elevated levels of serum interleukin-2. A gluten food challenge combined with interleukin-2 assessment could be valuable clinical tool for monitoring and diagnosing celiac disease in patients established on a gluten-free diet. Alimentary Pharmacology & Therapeutics
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Celiac.com 04/08/2015 - The goal of growth-monitoring programs in children is the early detection of any disorders that affect growth. Celiac disease is under-diagnosed in kids whose symptoms include faltering linear growth, short stature, or poor weight gain. A team of researchers recently set out to develop new evidence-based parameters for screening for growth disorders and to evaluate the performance of these cutoffs among children with celiac disease measured regularly in a nationwide growth screening program. The research team included Antti Saari, MD; Samuli Harju, BM; Outi Mäkitie, MD, PhD; Marja-Terttu Saha, MD, PhD; Leo Dunkel, MD, PhD; and Ulla Sankilampi, MD, PhD. They are variously affiliated with the Department of Pediatrics, School of Medicine, University of Eastern Finland, Kuopio, the Children’s Hospital at the University of Helsinki and Helsinki University Hospital in Helsinki, Finland, the Folkhälsan Research Centre in Helsinki, Finland, the Department of Molecular Medicine and Surgery at the Karolinska Institute in Stockholm, Sweden, the Department of Pediatrics at Tampere University Hospital in Tampere, Finland, the Centre for Endocrinology at the William Harvey Research Institute of Barts and the London School of Medicine and Dentistry at Queen Mary University of London in London, England and the Department of Pediatrics at Kuopio University Hospital, Kuopio, Finland. Their longitudinal retrospective study included growth data of healthy children from primary health care providers, and children with celiac disease from primary health care, and three university hospital outpatient clinics in Finland, Kuopio University Hospital, Tampere University Hospital, and Helsinki University Hospital, from January 1, 1994, to April 9, 2009. Children of the reference population were under 20 years of age, while children in the celiac disease group were between 1 and 16 years of age. In the reference population of 51,332 healthy children, the team screened according to five age- and sex-specific growth parameters: height standard deviation score and body mass index standard deviation score, distance from the population mean, distance from target height, change in height standard deviation score, and change in body mass index standard deviation score. They evaluated these parameters and their combination in 177 children with celiac disease by analyzing longitudinal growth data from birth until diagnosis of celiac disease. They measured the screening accuracy for detecting abnormal growth in children with celiac disease by using receiver operating characteristics analysis expressed as the area under the curve. When the team screened using the combination of all 5 growth-screening parameters, they detected celiac disease with good accuracy ([95% CI] = 0.88 [0.84–0.93] for girls and 0.84 [0.77–0.91] for boys). When they set the screening specificity at 90%, they saw abnormal growth in 57% of the girls with celiac disease, and in 48% of the boys with celiac disease for two years prior to diagnosis. This study shows that most kids with celiac disease experience faltering growth prior to diagnosis. An effective growth-monitoring program could have detected celiac disease in these kids several years earlier. By using several growth-monitoring parameters in combination, preferably using computerized screening algorithms that are integrated into an electronic health record system, researchers can improve sreening accuracy. Source: JAMA Pediatr. 2015;169(3):e1525. doi:10.1001/jamapediatrics.2015.25.
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Celiac.com 12/28/2009 - A team of researchers recently set out to compare continual monitoring of intraepithelial lymphocyte immunophenotype and clonality against snapshot analysis in the surveillance of refractory celiac disease. The research team was made up of H. Liu, R. Brais, A. Lavergne-Slove, Q. Jeng, K. Payne K, H. Ye, Z. Liu, J. Carreras, Y. Huang, C. M. Bacon, R. Hamoudi, V. Save, L. Venkatraman, P. G. Isaacson, J. Woodward, and M. Q. Du of Addenbrooke's Hospital, Cambridge, UK. Often, people with refractory celiac disease suffer from abnormal immunophenotype and monoclonality of intraepithelial lymphocytes (IELs). No good studies have been done to compare the utility of continual monitoring of IEL immunophenotype and clonality in monitoring refractory celiac disease (RCD). To address this deficiency, and to gather some data for comparison, the team used CD3e/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged TCR genes to evaluate diagnostic and follow-up biopsies from 33 people with proven celiac disease, 7 with suspected refractory celiac disease, 41 with proven refractory celiac disease, and 20 with enteropathy associated T-cell lymphoma (including 11 evolved from RCD). The team found aberrant immunophenotype (CD3epsilon(+)CD8(-) IEL >/=40%) and monoclonality in occasional celiac disease biopsies, either transiently in celiac patients not following a gluten free diet, or in those who later developed refractory celiac disease, suspected RCD, or enteropathy associated T-cell lymphoma (EATL). By comparison, they found aberrant immunophenotype and monoclonality respectively in 30 of 41 (73%) and 24 of 37 (65%) biopsies at the time of diagnosis for refractory celiac disease. Among the patients with refractory celiac disease showed no such abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases showed aberrant immunophenotype and monoclonality respectively upon follow-up. Whether found in initial or follow-up biopsies, the ongoing development of both aberrant immunophenotype and monoclonality is a common facet of refractory celiac disease. One key point was that the presence of both persistent monoclonality and aberrant immunophenotype, especially <>/=>80% CD3epsilon(+)CD8(-) IEL, was a strong predictor of enteropathy associated T-cell lymphoma development in patients with RCD (P=0.001). From these findings, the team found concludes that the continual monitoring of both immunophenotype and clonality of IEL is superior to snapshot analysis for diagnosis and follow-up of refractory celiac disease, and could provide a useful tool for surveillance of patients at risk of developing EATL. Source: Gut. 2009 Dec 8.
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Celiac.com 11/03/2008 - Blood testing for radioimmunoassay (RIA) tissue transglutaminase auto-antibodies (tTG-Abs) has proven to be a sensitive test for celiac disease follow-up. Recent studies have shown that RIA can accurately detect tTG-Abs in human saliva. However, not much is known about reliability of this method for monitoring the progress of celiac disease over time in patients who are attempting to follow a gluten-free diet. A team of researchers recently set out to assess salivary RIA tTG-Abs in celiac children on gluten-free diet. The research team included doctors M. Bonamico, R. Nenna, R.P.L. Luparia, C. Perricone, M. Montuori, F. Lucantoni, A. Castronovo, S. Mura; A. Turchetti, P. Strappini, and C. Tiberti. The team evaluated blood and saliva samples taken from 109 children at the time of their diagnosis for celiac disease. The first group included 71 females, with an average age of 9.4 years. A second group included 58 people who were following a gluten-free diet. The second group was broken into two subgroups: group 2a with 36 patients assessed at 3-6 months; and group 2b with 34 patients at 9 months or more (group 2b). The research team also included two control groups matched for age and sex. Group 3 included 89 gastroenterological patients, while group 4 included 49 healthy subjects. The team used RIA to detect tTG-Abs in saliva and blood, and compared the results against two other established tests: serum tTG-Abs ELISA and IgA anti-endomysium antibodies (EMA). The team detected salivary RIA tTG-Abs in 94.5% of patients from group 1, 66.7% of celiac patients from group 2a, and 50.0% from 2b. They detected blood RIA tTG-Abs in 98.2% of patients from group 1, 72.2% of celiac patients from group 2a, and 50.0% from 2b. The longer patients were on a gluten-free diet, the more the tTG-Abs decreased. The research team also found a correlation between saliva and serum levels (r = 0.75, P = 0.0001). A celiac disease follow-up showed comparable salivary and serum RIA sensitivities, and higher levels for EMA and ELISA methods. The research team concluded that it is possible to measure salivary tTG-Abs with a high level of accuracy; both at initial diagnosis for celiac disease, and also while patients are following a gluten-free diet. This discovery means that doctors treating people with celiac disease might soon be able to use a simple saliva test to monitor the progress of their patients’ gluten-free diets. Such a development might take remove much of the guesswork for celiacs who are trying to follow a gluten-free diet, and would be particularly useful for patients who might be asymptomatic, or who are at risk for celiac-associated conditions. Aliment Pharmacol Ther. 2008; 28(3): 364-370.
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