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Celiac.com 11/02/2021 - Lactobacillus strains L. plantarum HEAL9 and L. paracasei 8700:2 have shown anti-inflammatory properties by reducing the body's pro-inflammatory responses to antigens. Using a randomized double-blind placebo-controlled trial, a team of researchers recently set out to test the hypothesis that the two strains suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet. The research team included Åsa Håkansson; Carin Andrén Aronsson; Charlotte Brundin; Elin Oscarsson; Göran Molin; and Daniel Agardh. They are variously affiliated with the Department of Food Technology Engineering and Nutrition, Lund University in Lund, Sweden; and the The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 21428 Malmö, Sweden. The team enrolled a total of seventy-eight children with celiac disease autoimmunity. For six months, forty of the children received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group), while 38 children received a placebo containing maltodextrin. Using blood samples drawn at zero, three and six months, the team measured phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG). They found that naïve CD45RA+ Th cells decreased in the placebo group, while effector and memory CD45RO+ Th cells, and cells expressing CD4+CD25highCD45RO+CCR4+ increased. They also saw changes in the NK cells and NKT cells between the groups. Compared to the placebo group, the probiotic group saw average levels of IgA-tTG increase more substantially over time, while average levels of IgG-tTG decreased. Their results show that daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 reduces the intensity of the peripheral immune response in children with celiac disease autoimmunity. Read more in Nutrients 2019, 11(8), 1925

Celiac.com 07/27/2020 - Immunogenic gluten peptides that resist gastrointestinal breakdown are the main triggers for celiac disease. Gluten degrading enzymes represent a promising treatment option for managing celiac disease, but need to meet certain conditions within the gut to render gluten harmless before it reaches the duodenum. A team of researchers recently set out to review oral, gluten-degrading enzymes meant for use by celiacs on a gluten-free diet, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. The research team included Guoxian Wei, Eva J Helmerhorst, Ghassan Darwish, Gabriel Blumenkranz, and Detlef Schuppan. They are variously affiliated with the Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston, MA, USA; the Institute for Translational Immunology and Research Center for Immunotherapy (FZI), Johannes Gutenberg University (JGU) Medical Center in Mainz, Germany; and the Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Most people with celiac disease are exposed to trace amounts of gluten on a regular basis. Whether due to high sensitivity or repeated exposure, many celiac patients continue to suffer both symptoms and damage despite following a gluten-free diet. In addition to simplified testing for ongoing gluten-exposure, there's a pressing need for safe treatments that can help address the realities of gluten-exposure by those on a gluten-free diet. Gluten-degrading enzymes are one especially promising option. To be effective, such enzymes would need to be safe for people, active under gastro-duodenal conditions, and rapidly neutralizing T cell activating gluten peptides. Gluten peptides normally resist digestion, but a number of enzymes, including bacterial, fungal and plant derived glutenases, especially food-grade subtilisins (Sub-A), prolyl endopeptidases (PEP), AN-PEP enzymes, barley seed derived glutamine-specific cysteine endoprotease (EP-B2) and synthetic glutenases (Kuma030) are all potential game changers for oral enzyme therapy for people with celiac disease. Researchers have had some success with various combinations of enzymes, molecular modeling and chemical modifications, such as PEGylation, enteric coatings or enzyme carriers. The goal is to develop a product that can quickly and completely break down immunogenic gluten peptides that are bound up in foods. The digestion of gluten peptides must happen fully within the stomach and proximal small intestine before these peptides reach the mucosal immune system of the small intestine. Without exception, these enzymes must function in the glutamine- and proline-rich environments of antigenic gluten peptides. Such enzymes also need to remain stable in stomach acid, and in the near neutral pH in the duodenum. According to the researchers: "Bacterial, fungal and plant derived glutenases, especially (food-grade) subtilisins (Sub-A), prolyl endopeptidases (PEP), barley seed derived glutamine-specific cysteine endoprotease (EP-B2) and synthetic glutenases (Kuma030) are considered promising candidates for an (adjunctive) oral enzyme therapy. " The team's recent review acknowledges the potential for oral enzymes in improving celiac disease treatment, and focuses on the origins and actions, clinical evaluations and therapeutic challenges faced by enzymes intended to treat celiac disease. Read more at: MDPI.com

Celiac.com 07/13/2020 - Celiac disease is a systemic disease that damages the small intestine and which, left untreated, can lead to numerous related health problems. The only treatment for celiac disease remains a gluten-free diet. Celiac disease is classified as an autoimmune disease in part because of the presence of anti-tissue transglutaminase 2 (anti-TG2) antibodies in the serum, as well as the presence of other autoimmune features. Anti-TG2 autoantibodies are produced in the intestines, and they show up there even before they begin to circulate in the blood. Researchers Mariantonia Maglio and Riccardo Troncone of the Department of Medical Translational Sciences and European Laboratory for the Investigation of Food-Induced Diseases at the University Federico II in Naples, Italy, recently set out to see what they might be able to learn about celiac disease autoimmunity by looking at intestinal anti-tissue transglutaminase2 autoantibodies. Exactly how these antibodies are generated is still poorly understood, but gliadin-specific T cells seem to play a significant role. The team noted some somatic mutations in VH and VL genes in TG2-specific plasma cells, along with a major reliance on a heavy chain encoded by the VH5 gene. However, previous studies on the effect of anti-TG2 antibodies on TG2 function have produced variable data. Anti-TG2 antibodies in the blood is a major indicator of celiac disease, but their role in the development of the celiac lesion remains unclear. Researchers have taken various approaches to detect and measure the production of intestinal celiac-associated autoantibodies. Anti-TG2 antibodies may predict full-blown enteropathy in potential celiac patients. They also show potential for revealing gluten-reactivity in patients without circulating celiac-associated autoantibodies. Celiac disease-specific autoantibody production in the intestine, in patients who test negative for the same antibodies, may be among the first signs of early gluten reactivity. Or, if not specific for celiac disease, it might be a result of intestinal inflammation. The importance of mucosal anti-TG2 antibodies in the development of celiac disease remains unclear. The presence of mucosal anti-TG2 antibodies, the way they are produced, and their dependence on gluten make them promising targets for studying autoimmunity. Read more at: Front Nutr. 2020; 7: 73

Celiac.com 06/19/2020 (Revised 06/24/2020) - It is not uncommon to have received blood testing from your doctor to see if you have celiac disease, and it comes back negative, when in fact your body is actually having a problem and you are on the celiac spectrum. The tests most doctors use to determine whether or not someone has celiac disease are very accurate for end stage celiac disease-after you have total villous atrophy, but not earlier stages of the disease (1). In those earlier situations, these tests often come back negative, even though you truly have a problem and are reacting to wheat moving towards total villous atrophy (1, 2, 3, 4, 5). It’s the wrong test. If you have an earlier stage in terms of the amount of damage incurred, the standard blood tests can be wrong over 70% of the time giving false negatives Standard blood tests for celiac disease have been extremely accurate and dependable if a person has total villous atrophy celiac disease. However, the accuracy of the blood test results for the two accepted blood markers (Endomysium and Tissue Transglutaminase) with anything less than total villous atrophy drops tremendously (to as low as being wrong 7 out of 10 times) (8,9). The reason these tests are often wrong in some people is that the research to validate the test used subjects who all had been diagnosed with celiac disease which by definition was total villous atrophy (Marsh IIIa,b,c). The earlier stages, Marsh 1 and 2 by most are considered ‘potential celiac disease’. So, when researchers were looking to validate if their blood tests were accurate in diagnosing celiac disease, they tested the blood of people diagnosed with celiac disease (total villous atrophy). And in that scenario, endomysium and tissue transglutaminase are highly accurate. from Lerner A, Jeremias P, Neidhöfer S, Matthias T (2017) Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage. J Clin Cell Immunol 8: 486. from Lerner A, Jeremias P, Neidhöfer S, Matthias T (2017) Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage. J Clin Cell Immunol 8: 486. Why? Celiac disease is defined as total villous atrophy. However, you don’t just magically go to sleep one night fine and wake up the next morning with total villous atrophy celiac disease. This disease, like all diseases, needs to be looked at more as a spectrum. That’s why Prof. Michael Marsh identified the spectrum of celiac disease development (Marsh I, II, III a, b, c). Bottom line? The test for total villous atrophy celiac disease (Marsh III a, b, c) are not the tests to rely on for earlier phases of the spectrum (Marsh I, II). The end result is many people have been told they do not have celiac disease and wheat is not a problem continue eating this food that is leading them further down the path of autoimmune disease. And of course, the tests for celiac disease are NOT the tests for the spectrum of Wheat Related Disorders (9). Predictive autoimmunity can tell you what areas of your body are under attack. Identifying an autoimmune mechanism early in the spectrum of development gives an opportunity to address it before there is so much tissue damage, now you have an autoimmune disease. Autoimmunity is the number 3 cause of death and highly preventable. If you could peek inside and determine what is going on before it does irreparable damage, it gives you a window of opportunity to address the problem early on and change the course of your health. This is called Predictive Autoimmunity (30). Identifying that you are on the celiac spectrum at Marsh I, gives you the opportunity to take action (gluten-free diet) and prevent progressing to Marsh III total villous atrophy. So the tests that are highly accurate for Marsh III are the wrong tests for Marsh I and II. They may be helpful and they may be misleading Gluten, Autoimmunity, and Your Gut Dr. Alessio Fasano is the chair of pediatric gastroenterology at Mass. General Hospital, Harvard, and director of Mucosal Immunology and Biology Research Center at Mass General Hospital for Children. He has done extensive research in the area of mucosal lining of the gut. He discovered, in the early 2000’s, a trilogy present in the development of autoimmunity: genetics, triggers, and intestinal permeability. (10) With celiac, we all know this – DQ2/DQ8, gluten, leaky gut = vulnerability to developing celiac disease. In the last 15 years, research has continued to expand to include two more features - thus a total of 5 components in the development of autoimmune diseases. In addition to genetics, environmental triggers and intestinal permeability, we now know that a dysbiotic microbiome and a systemic inflammatory immune response are involved. (11) This is important in our understanding of treatment. You can arrest the development of autoimmunity by healing the gut and addressing intestinal permeability. The majority of people with leaky gut do not show symptoms in the gut. A leaky gut spews out macromolecules into the blood stream that travel throughout your body that are considered foreign objects that your immune system will protect you from. And the resulting systemic inflammation from a leaky gut can affect any area of your body. And what are the most common triggers that will trigger a leaky gut? Gluten and small intestinalal bacteria overload. (11) Dangers of a Gluten-Free Diet Now this is a ‘Big Picture’ concept, but when you read the science it is clear that no one can fully digest the proteins in wheat (11, 12, 13, 14). It is indigestible to all humans, and in every single person causes a transient state of intestinal permeability (12, 13). Having said that, not everything about wheat is bad. Wheat (78%) and barley (3%) account for 78 - 81% of total prebiotics in the Western diet (14, 15, 16). When you remove wheat from your diet, a large percentage of the good bacteria will likely starve. This may be a contributing factor to the jaw-dropping statistic from the largest study ever done on mortality and celiac disease, that being diagnosed with celiac disease is associated with an 86% increased risk of mortality from a cardiovascular incident within 1 year (18). Just by being diagnosed. As far as I know, no one has pursued further research on this fact. What is different after diagnosis? People go on a gluten-free diet. What else? For most people, nothing else-they just stat eating gluten-free foods. You MUST be conscious of replacing the loss of prebiotics in your diet. Replacing wheat-based products with gluten-free products is a landmine. The vast majority of gluten-free products do not have prebiotic fibre, are not enriched, and are just tasty white paste. There’s nothing wrong with a gluten-free blueberry muffin once in a while, or gluten-free pasta on occasion. But these products are not healthy for you and can NOT be the cornerstone of your new diet. Be mindful of this at the onset of starting your gluten-free diet, so that you replenish your body with the necessary prebiotic nutrients your microbiome needs to increase diversity and balance. (14) So many people make the same newbie mistakes of just shopping in the gluten-free aisle and walk away with gluten-free cookies and snacks. I’m sorry to say that those are pretty much just as unhealthy, or worse, than the gluten versions. They just lack the antigen gluten. You need to look towards the produce aisle, vary your food choices from day to day, eat a wide variety in colour and types of organic fruits and vegetables, eat fermented foods rich in probiotics, and feed that good bacteria in your gut with foods that are prebiotics (root vegetables daily). I highly recommend finding a Certified Gluten-free Practitioner (CGP) who has received extensive training in celiac disease, gluten sensitivities, wheat-related disorders and autoimmunity. That is the most comprehensive training out there in this area. Find a CGP in your area-they’re all over the world, and most do on-line private consults. Addressing the intestinal permeability that has been developing with every exposure to wheat (12), within 5 minutes of wheat coming out of the stomach into the small intestine (20), is a game-changer in your overall health. There are over 300 autoimmune conditions. With the ‘Gateway’ in the development of autoimmune diseases being intestinal permeability, addressing this, and focusing on healing the gut can bring big rewards. Heal the Gut Identify and eliminate your triggers. Reduce inflammation. Reduce stress. The following supplements all have many studies showing their value in addressing intestinal permeability: Glutamine (21), Fish oils (22), Vitamin D (23), Colostrum (24), Turmeric (25), Pre (26) and Probiotics (27). Each of these basic nutrients modulates (has their hands on the steering wheel) of genes to reduce inflammation achieving a similar end goal, but they each work in different ways. Using a pleiotropic approach ensures success (great scrabble word-pleiotropic-means ‘all roads lead to Rome’. When you have a gluten-related disorder, the treatment is a strict gluten-free diet - without exception. Don’t let the treatment be the trigger for more problems. I’m known for the saying “You can’t be a little pregnant, you can’t have a little gluten” (if your immune system is activated fighting any of the peptides of wheat). Cheating once-per-month increases your risk of early death 6-fold! (19) Take measures to protect yourself against nutritional and vitamin deficiencies associated with a gluten-free diet. The benefits of a ‘Coach’ to learn the correct basics through this transition cannot be overemphasized (28, 29). A CGP, Nutritionist, trained Registered Dietician, Health Coach, … are invaluable in you learning the basics of this transition into a new way of eating. Eat different colors of the rainbow at every meal, every day. It will help restore balance to your gut health and rebalance your immune system. If you’re going to do this alone, avoid wheat (gluten), dairy, and added sugar for a month. Eat nutrient dense organic foods, such as quinoa, amaranth, vegetables, and quality meats. Gauge how you feel. Is your weight better managed? Do your hands and feet no longer feel cold? Are you able to think more clearly? If so, continue to eliminate those offending foods and eat a varied diet rich in nutrients. If you reintroduce and notice a problem, now you know those were foods that are inflammatory to you. And be careful of your tricky mind. Humans are the only species on the planet that finds something that works, and they stop doing it! References: Lerner A, Jeremias P, Neidhöfer S, Matthias T (2017) Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage. J Clin Cell Immunol 8: 486 Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease. Salmi TT, Collin P, Järvinen O, Haimila K, Partanen J, Laurila K, Korponay-Szabo IR, Huhtala H, Reunala T, Mäki M, Kaukinen K.Aliment Pharmacol Ther. 2006 Aug 1;24(3):541-52 Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease. Brar P, Kwon GY, Egbuna II, Holleran S, Ramakrishnan R, Bhagat G, Green PH.Dig Liver Dis. 2007 Jan;39(1):26-9 Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy. Abrams JA, Diamond B, Rotterdam H, Green PH.Dig Dis Sci. 2004 Apr;49(4):546-50 Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of celiac disease. Abrams JA, Brar P, Diamond B, Rotterdam H, Green PH.Clin Gastroenterol Hepatol. 2006 Jun;4(6):726-30 Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis. Silvester JA, Kurada S, Szwajcer A, Kelly CP, Leffler DA, Duerksen DR.Gastroenterology. 2017 Sep;153(3):689-701 Screening for celiac disease.Lebwohl B, Green PH.N Engl J Med. 2003 Oct 23;349 (17):1673-4 Joint BAPEN and British Society of Gastroenterology Symposium on 'Coeliac disease: basics and controversies'. Coeliac disease in the twenty-first century. Dickey W. Proc Nutr Soc. 2009 Aug;68(3):234-41. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Fasano A, Shea-Donohue T. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22. Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020;9:F1000 Faculty Rev-69. Published 2020 Jan 31. doi:10.12688/f1000research.20510.1. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. Leonard MM, Sapone A, Catassi C, Fasano A. JAMA. 2017 Aug 15;318(7):647-656. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A.Nutrients. 2015 Feb 27;7(3):1565-76. Lerner A, O'Bryan T, Matthias T. Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet. Front Pediatr. 2019;7:414. Published 2019 Oct 15. Effects of a gluten-free diet on gut microbiota and immune function in healthy adult Human subjects - comment by Jackson. Jackson FW. Br J Nutr. 2010 Sep;104(5):773. On the presence of Inulin and Oligofructose as natural ingredients in the western diet Jan Van Loo , Paul Coussement , Leen De Leenheer , Hubert Hoebregs & Georges Smits Critical Reviews in Food Science and Nutrition, Volume 35, 1995 - Issue 6. Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, Cani PD, Larondelle Y, Delzenne NM. PLoS One. 2011;6(6):e20944. Small-intestinal histopathology and mortality risk in celiac disease. Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F., JAMA. 2009 Sep 16;302(11):1171-8. Mortality in patients with coeliac disease and their relatives: a cohort study. Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, Sategna Guidetti C, Usai P, Cesari P, Pelli MA, Loperfido S, Volta U, Calabró A, Certo M; Club del Tenue Study Group.Lancet. 2001 Aug 4;358(9279):356-61. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, Bethge J, Böttner M, Klose J, Milla. PJ.Gastroenterology. 2014 Nov;147(5):1012-20. Glutamine and the regulation of intestinal permeability: from bench to bedside. Achamrah N, Déchelotte P, Coëffier M.Curr Opin Clin Nutr Metab Care. 2017. Jan;20(1):86-91 Potential of Omega-3 Polyunsaturated Fatty Acids in Managing Chemotherapy- or Radiotherapy-Related Intestinal Microbial Dysbiosis. Zhang Y, Zhang B, Dong L, Chang P.Adv Nutr. 2019 Jan 1;10(1):133-147. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC.Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16. Peptide Immunotherapy: Colostrum, A Physician's Reference Guide Hardcover, Keech A., AKS Publishing; 1St Edition edition (2009) ISBN-10: 0692002421. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Aggarwal BB, Harikumar KB.Int J Biochem Cell Biol. 2009 Jan;41(1):40-59. Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome. Delzenne NM, Neyrinck AM, Cani PD.Microb Cell Fact. 2011 Aug 30;10 Suppl 1(Suppl 1):S10 Gut Microbiota in Celiac Disease: Is There Any Role for Probiotics? Pecora F, Persico F, Gismondi P, Fornaroli F, Iuliano S, de'Angelis GL, Esposito S.Front Immunol. 2020 May 15;11:957. Factors that influence adherence to a gluten-free diet in adults with celiac disease. Leffler DA, Edwards-George J, Dennis M, Schuppan D, Cook F, Franko DL, Blom-Hoffman J, Kelly CP.Dig Dis Sci. 2008 Jun;53(6):1573-81. Gluten-free diet: the medical and nutrition management of celiac disease. See J, Murray JA.Nutr Clin Pract. 2006 Feb;21(1):1-15. Predicting and preventing autoimmunity, myth or reality? Harel M, Shoenfeld Y.Ann N Y Acad Sci. 2006 Jun;1069:322-45.

06/08/2020 - Many doctors and celiac patients have found that a gluten-free diet seems to improve some autoimmune diseases associated with celiac disease. A team of researchers recently set out to determine the effect of a gluten-free diet on autoimmune pituitary impairment in patients with celiac disease and potential/subclinical lymphocytic hypophysitis (LYH) by conducting a five-year longitudinal observational study. The research team included Giuseppe Bellastella, Maria Ida Maiorino, Paolo Cirillo, Miriam Longo, Vlenia Pernice, Angela Costantino, Carmen Annunziata, Antonio Bellastella, Katherine Esposito, and Annamaria De Bellis. They are variously affiliated with University of Campania “Luigi Vanvitelli,” in Naples, Italy; the Unit of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli,” in Naples, Italy; the Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy; and the Unit of Diabetes, University of Campania “Luigi Vanvitelli,” Naples, Italy. The study took place in the tertiary referral center for immunoendocrinology at the University of Campania “Luigi Vanvitelli.” In all, from 2000 to 2013, the team assessed ninety-three newly diagnosed LYH patients, with high titer of antipituitary antibodies [APA], and a second group with normal or subclinically impaired pituitary function. The first group included 43 patients with LYH and celiac disease. The second group included 50 patients with just isolated LYH. Patients diagnosed with celiac disease initiated a gluten-free diet. The team assessed APA titers and pituitary function in both groups at the start of the study, and then every year for 5 years. The team did not follow-up on patients who developed clinically overt LYH. Nearly 35% of patients in group 1 experienced remission of LYH (defined as the disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism). Just a single patient (2% of total) in group 2 experienced remission. Two patients in group 1 and 25 in group 2 developed clinically overt hypopituitarism, and left the study to receive appropriate therapy. The big takeaway here is that the presence of celiac disease was the only independent predictor of pituitary function recovery. A gluten-free diet helps a significant number of patients with LYH and celiac disease to achieve remission of subclinical LYH, or prevent disease progression to more severe stages. Stay tuned for more on this and related stories. Read more at the Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 7, July 2020

Celiac.com 09/17/2019 - Celiac disease is associated with psychopathology in children. However, it's unknown whether this connection is present in children with celiac disease autoimmunity identified by screening. A team of researchers recently set out to examine the associations between sub-clinical celiac disease autoimmunity and emotional and behavioral problems in children without a previous celiac disease diagnosis. The research team included Rama J. Wahab, Sytske A. Beth, Ivonne P.M. Derks, Pauline W. Jansen, Henriëtte A. Moll, and Jessica C. Kiefte-de Jong. As part of a population-based cohort study, the team analyzed levels of tissue transglutaminase autoantibodies in 3,715 children averaging 6 years of age. After excluding children with diagnosed celiac disease or those on a gluten-free diet, the team found 51 children with celiac disease autoimmunity, defined as levels of tissue transglutaminase autoantibodies at or above 7 U/mL. To assess behavioral and emotional problems of children averaging 5.9 years old, they used a Child Behavior Checklist (CBCL) completed by the parents. They applied multiple linear regression models to assess the cross-sectional connections between celiac disease autoimmunity and CBCL scores. They also conducted sensitivity analyses in a subgroup of seropositive children with HLA antigen risk alleles for celiac disease. The data showed that celiac disease autoimmunity, especially combined with the HLA-DQ2 and HLA-DQ8 risk alleles, is associated with anxiety problems and oppositional defiant problems. The team is calling for more research to determine whether behavioral problems might be an indication of sub-clinical celiac disease. Read more in Pediatrics The researchers are variously affiliated with the Generation R Study Group; the Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands; the Departments of Child and Adolescent Psychiatry and Psychology; the Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands; and the Department of Public Health and Primary Care, Campus The Hague, Leiden University Medical Center, The Hague, Netherlands.

Celiac.com 08/26/2019 - Does the amount of gluten consumed during the first 5 years of life influence the risk of celiac disease autoimmunity and celiac disease in at-risk children? A new study says it does. There's been some previous study data to suggest that high gluten intake during childhood may increase risk of celiac disease. A team of researchers working for The Environmental Determinants of Diabetes in the Young (TEDDY) study group recently set out to investigate if gluten intake levels are associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. The TEDDY group is a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease. The research team included Carin Andrén Aronsson, PhD; Hye-Seung Lee, PhD; Elin M. Hård af Segerstad, MSc; et al Ulla Uusitalo, PhD; Jimin Yang, PhD; Sibylle Koletzko, MD, PhD; Edwin Liu, MD, PhD; Kalle Kurppa, MD, PhD; Polly J. Bingley, MD; Jorma Toppari, MD, PhD; Anette G. Ziegler, MD; Jin-Xiong She, PhD; William A. Hagopian, MD, PhD; Marian Rewers, MD, PhD; Beena Akolkar, PhD; Jeffrey P. Krischer, PhD; Suvi M. Virtanen, MD, PhD; Jill M. Norris, MPH, PhD; Daniel Agardh, MD, PhD; for the TEDDY Study Group For their multinational prospective birth study, the team looked at gluten consumption in 6,605 genetically predisposed children in 6 clinical centers in Finland, Germany, Sweden, and the United States. The team defined celiac disease autoimmunity as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The team defined celiac disease as cases confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. The team estimated gluten intake from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Their results showed that children with higher gluten intake levels had a significantly higher risk of celiac disease autoimmunity, with an absolute risk difference of 6.1%. Children with higher gluten intake levels also had a significantly higher risk of celiac disease, with an absolute risk difference of 7.2%, for every gram increase of gluten intake per day. This study shows that genetically predisposed children with higher gluten intake during the first 5 years of life face an increased risk of celiac disease autoimmunity and celiac disease. Read more at JAMA. 2019;322(6):514-523. doi:10.1001/jama.2019.10329 The researchers are variously affiliated with the Department of Clinical Sciences, Lund University, Malmö, Sweden; the Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa; the Dr von Hauner Children’s Hospital, Ludwig Maximilians University, Munich, Germany; the University of Warmia and Mazuri, Olsztyn, Poland; the Digestive Health Institute, University of Colorado Denver, Children’s Hospital Colorado, Denver; the Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland; the School of Clinical Sciences, University of Bristol, Bristol, England; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland; the Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes eV, Neuherberg, Germany; the Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia; Pacific Northwest Diabetes Research Institute, Seattle, Washington; the Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora; the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; the National Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland; the Faculty of Social Sciences/Health Sciences, University of Tampere, Tampere, Finland; the Research Center for Child Health, Tampere University, University Hospital, Science Center of Pirkanmaa Hospital District, Tampere, Finland; and the Colorado School of Public Health, Department of Epidemiology, University of Colorado, Aurora, Colorado.

Celiac.com 05/16/2019 - People with potential celiac disease show positive results from blood tests for tissue transglutaminase antibodies (anti-TG2), but show no damage to the intestinal lining. Such patients are all Marsh stage 0 or 1, meaning they have healthy, normal gut mucosa. Clinicians are still sorting out the best way to treat these patients. To provide some answers, a team of researchers recently set out to assess risk factors for villous atrophy in children with potential celiac disease. The team included R. Auricchio, R. Mandile, M.R. Del Vecchio, S. Scapaticci, M. Galatola, M.A. Maglio, V. Discepolo, E. Miele, D. Cielo, R. Troncone, and L. Greco. They are variously affiliated with the Department of Translation Medical Science, Section of Pediatric, and European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy, and the Department of Medicine, University of Chicago, Chicago, IL, USA. For children with "potential" celiac disease who do not follow gluten-free diets, possible risk factors for villous atrophy include age at diagnosis, gamma delta lymphocytes and HLA haplotype, researchers say. The team conducted a prospective study of 280 children between 2–18 years old in Italy who had suspected celiac disease, and followed the children from 18 months to 12 years. Each participant had two consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of IgA in the normal range, normal Marsh 0–1 duodenal condition in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy every 2 years. Two hundred ten patients of the original group were checked after 9-years. The team conducted multivariate analyses of clinical, genetic, and histologic data to spot factors associated with villous atrophy. The team's long-term study showed 43% cumulative rates of progression to villous atrophy over the 12-year study. The team identified factors that can be used to spot children with the highest risk for villous atrophy. This approach might be used to assess whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet. The takeaway, Dr. Auriccio told reporters, is that potential celiac disease affects "a very heterogenous group of patients [who]...have to be carefully managed by expert pediatric gastroenterologists." Studies like this one by Dr. Auriccio and his team are highly valuable, because diagnosing and properly treating celiac disease as early as possible is important in helping to prevent the development of associated conditions later on. Read more at Gastrojournal.org

Celiac.com 10/29/2018 - Researchers Emma L. Smith with UCB Pharma Ltd., Slough, United Kingdom, and Mark Peakman from the Department of Immunobiology, King’s College London, London, United Kingdom recently set out to catalog clinical advances in peptide immunotherapy for Type 1 diabetes. Autoimmune and allergic diseases occur when a person’s body has an incorrect immune response to an antigen from the person’s own body, or to an innocuous antigen from outside the body. This triggers a pathogenic T-cell response which causes damage to certain tissues and organs. In Type 1 diabetes, this process results in the destruction of the insulin-secreting β cells, which leads to permanent need for recombinant insulin to make up for the loss. The best way to restore immune homeostasis and prevent further tissue damage is to reduce or cease the pathogenic T-cell response by using antigen-specific peptide immunotherapy. Smith and Peakman found that recent clinical advances with peptide therapy approaches in both Type 1 diabetes and other diseases are beginning to show encouraging results. New treatments that target peptides specific to certain cell types are also moving from the development stages into clinical use. Drug developers still face numerous hurdles in reaching full clinical use, including determining optimal dose and dosing frequency, but peptide immunotherapy for Type 1 diabetes is clearly becoming a very active field of drug development. Read their full report: Front Immunol. 2018; 9: 392.Published online 2018 Feb 28. doi:  10.3389/fimmu.2018.00392PMCID: PMC5836708PMID: 29541078

Celiac.com 03/26/2018 - Researchers are making serious headway in understanding critical aspects of celiac disease and other autoimmune conditions. However, despite numerous studies showing links between gut microbiota and immune diseases, researchers still don’t know very much about role of gut microbiota in autoimmunity. One team of researchers recently found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. What does that mean, exactly, and what else did they find? First of all, it’s important to understand that a pathobiont is any potentially disease-causing organism which, normally, lives in symbiosis with its host. So, these are organisms that normally cause no problems at all, but which, under certain circumstances, can cause disease. The research team included S. Manfredo Vieira, M. Hiltensperger, V. Kumar, D. Zegarra-Ruiz, C. Dehner, N. Khan, F. R. C. Costa, E. Tiniakou, T. Greiling, W. Ruff, A. Barbieri, C. Kriegel, S. S. Mehta, J. R. Knight, D. Jain, A. L. Goodman, and M. A. Kriegel. They are variously affiliated with the Department of Immunobiology, the Department of Medicine, and the Department of Pathology, the Yale Center for Genome Analysis, the Department of Microbial Pathogenesis and Microbial Sciences Institute at the Yale School of Medicine in New Haven, CT, USA, the Department of Biochemistry and Immunology, Ribeirao Preto Medical School, Ribeirao Preto, SP, Brazil, the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA, and the Department of Dermatology, Oregon Health and Science University, Portland, OR, USA. The team’s study data for this model showed that antibiotic treatment prevented mortality, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells, while Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. Liver biopsies of autoimmune patients yielded E. gallinarum–specific DNA, while cocultures with human hepatocytes replicated the murine findings, which means that similar processes likely occur in susceptible humans. This study shows that a gut pathobiont can change locations and can promote autoimmunity in people with a genetic predisposition. This is an important revelation that will help researchers to better understand the mechanisms that trigger celiac disease, and may lead to better diagnosis and treatment options in the future. Source: Science  09 Mar 2018: Vol. 359, Issue 6380, pp. 1156-1161. DOI: 10.1126/science.aar7201

Celiac.com 01/15/2018 - Cerebellar ataxia with sensory ganglionopathy is a disabling combination of neurological dysfunction that usually occurs as part of certain hereditary ataxias. However, some patients present this combination with no apparent genetic cause. A team of researchers recently set out to if autoimmunity might have a role to play in SG. The research team included Panagiotis Zis, Ptolemaios Georgios Sarrigiannis, Dasappaiah Ganesh Rao, Nigel Hoggard, David Surendran Sanders, and Marios Hadjivassiliou. They are variously affiliated with the Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; the University of Sheffield, Sheffield, UK; the Department of Neuroradiology, Sheffield Teaching Hospitals NHS Foundaiton Trust, Sheffield, UK; the University of Sheffield, Sheffield, UK; and the Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. The team reviewed records of all patients that have been referred to the Sheffield Ataxia Centre who had neurophysiological and imaging data suggestive of SG and cerebellar ataxia respectively. We excluded patients with Friedreich's ataxia, a common cause of this combination. All patients were screened for genetic causes and underwent extensive investigations. They found 40 patients with combined cerebellar ataxia and sensory ganglionopathy. The majority of patients were initially diagnosed with cerebellar dysfunction, and about one-third were initially diagnosed with sensory ganglionopathy. For that one-third, the two diagnoses were made together. The average time between the two diagnoses was 6.5 ± 8.9 years, ranging from 0 up to 44 years. The most common initial symptom was unsteadiness, in 77.5% of patients, followed by patchy sensory loss in 17.5%, and peripheral neuropathic pain in 5%. Nineteen patients had gluten sensitivity, of whom 3 patients had biopsy proven celiac disease. Other abnormal immunological tests were present in another 15 patients. Six patients had malignancy, which was diagnosed within 5 years of the neurological symptoms. Only 3 patients were classified as having a truly idiopathic combination of cerebellar ataxia with sensory ganglionopathy. This study shows that immune pathogenesis plays a significant role in patients with the unusual combination of cerebellar ataxia and sensory ganglionopathy. Source: Cerebellum & Ataxias 20174:20

Celiac.com 11/07/2017 - Researchers still don't have much good data on the consequences of antibiotic use in early life and how that relates to the risk of certain autoimmune diseases. A team of researchers recently set out to test the association between early-life antibiotic use and islet or celiac disease autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or celiac disease. Their study is part of a larger study called The Environmental Determinants of Diabetes in the Young, or TEDDY, for short. The reasearch team enrolled HLA-genotyped newborns from Finland, Germany, Sweden, and the United States between November 20, 2004, and July 8, 2010, and analyzed data from November 20, 2004, to August 31, 2014. They also enrolled individuals from the general population, and those having a first-degree relative with T1D, with any 1 of 9 HLA genotypes associated with a risk for T1D. The team charted parental reports of the most common antibiotics, such as cephalosporins, penicillins, and macrolides, used between age 3 months and age 4 years. Islet autoimmunity and celiac disease autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. The team used Cox proportional hazards regression models to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity, and to calculate hazard ratios and 95% CIs. The team conducted tests for islet and tissue transglutaminase autoantibodies on 8,495 children (49.0% female), and 6,558 children (48.7% female) who were enrolled in the TEDDY study, and they found that antibiotic exposure and frequency of use in early life or before seroconversion did not influence the risk of developing islet autoimmunity or celiac disease autoimmunity. Additionally, cumulative use of any antibiotic during the first 4 years of life was not tied to the appearance of any autoantibody (hazard ratio , 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02). Using any of the most common antibiotics during the first 4 years of life, in any geographic region, did not influence the later development of autoimmunity for T1D or celiac disease. Based on these results, the team concluded that doctors recommending antibiotics for young children at risk for T1D or celiac disease need not be concerned that the use will lead to islet or tissue transglutaminase autoimmunity. Source: JAMA Pediatr. Published online October 9, 2017. doi:10.1001/jamapediatrics.2017.2905 The research team included Kaisa M. Kemppainen, PhD; Kendra Vehik, PhD; Kristian F. Lynch, PhD; Helena Elding Larsson, MD, PhD; Ronald J. Canepa, BSc; Ville Simell, MSc; Sibylle Koletzko, MD, PhD; Edwin Liu, MD; Olli G. Simell, MD, PhD; Jorma Toppari, MD, PhD; Anette G. Ziegler, MD, PhD; Marian J. Rewers, MD, PhD; Åke Lernmark, PhD; William A. Hagopian, MD, PhD; Jin-Xiong She, PhD; Beena Akolkar, PhD; Desmond A. Schatz, MD; Mark A. Atkinson, PhD; Martin J. Blaser, MD; Jeffrey P. Krischer, PhD; Heikki Hyöty, MD, PhD; Daniel Agardh, MD, PhD; and Eric W. Triplett, PhD; for The Environmental Determinants of Diabetes in the Young (TEDDY) Study Group. They are variously affiliated with the Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville; the Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa; the Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden; the MediCity Laboratory, University of Turku, Turku, Finland; the Division of Paediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Ludwig Maximilian University, München, Germany; the Digestive Health Institute, Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado Denver, Aurora; the Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; the Department of Pediatrics, University of Turku, Turku University Hospital, Turku, Finland; the Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland Institute of Diabetes Research, Helmholtz Zentrum München, München, Germany; the Klinikum Rechts der Isar, Technische Universität München, München, Germany; the Forschergruppe Diabetes e.V., Neuherberg, Germany; the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora; the Pacific Northwest Diabetes Research Institute, Seattle, Washington; the Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; the Department of Pediatrics, College of Medicine, University of Florida, Gainesville; the Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville; the Department of Medicine and Microbiology, New York School of Medicine, New York; the Department of Virology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; and with Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.

Celiac.com 03/13/2017 - A team of researchers recently set out to determine whether there might exist ethnic differences in celiac disease autoimmunity in children at 6 years of age, and if present, to assess how these differences may be explained by known sociodemographic and environmental factors. The research team included Michelle A E Jansen, Sytske A Beth, Diana van den Heuvel, Jessica C Kiefte-de Jong, Hein Raat, Vincent W V Jaddoe, Menno C van Zelm, and Henriette A Moll. They are variously affilated with the Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; the Department of Paediatrics, the Department of Immunology, and the Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and with the Department of Public Health, University Medical Center, Rotterdam, the Department of Global Public Health at Leiden University College, The Hague, The Netherlands, and with the Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Australia. The team embedded their study within a multi-ethnic population-based prospective cohort study of 4442 six-year-old children born between 2002 and 2006. They used questionnaires to assess information on ethnicity, environmental and lifestyle characteristics. They divided ethnicity into Western, which included Dutch, European, Indonesian, American, Oceanian, and non-Western, which included Turkish, Moroccan, Cape Verdean, Antillean, Surinamese. The team then used fluorescence enzyme immunoassay to measure serum transglutaminase type 2 antibody (TG2A) levels . They used ELISA to measure serum IgG levels against cytomegalovirus (CMV). They defined TG2A positivity as TG2A ≥7 U/mL, strong TG2A positivity as TG2A ≥10 upper limit normal (70 U/mL). Of the 4,442 children they assessed, just 60, or 1.4%, tested TG2A positive. Of these 60, 31 registered strong positive. In all, 66% of these children were Western, 33% non-Western. Western ethnicity, high socioeconomic position and daycare attendance were positively associated with strong TG2A positivity (odds ratio (OR) 6.85 (1.62 to 28.8) p Together, these factors explained up to 47% (−67 to −17; p=0.02) of the ethnic differences in TG2A positivity between Western and non-Western children. Ethnic differences in children with celiac disease autoimmunity are present in childhood. Socioeconomic position, daycare attendance and CMV seropositivity partly explained these differences, and may serve as targets for prevention strategies for CDA. Source: BMJ Publishing Group Limited

Celiac.com 10/13/2016 - Researchers don't currently know much about rates of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) in patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population. A team of researchers recently set out to assess rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The research team included Zhiyuan Zhao, Jing Zou, Lingling Zhao, Yan Cheng, Hanqing Cai, Mo Li, Edwin Liu, Liping Yu, and Yu Liu. The study included 178 patients with type 1 diabetes, along with 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy control subjects. The team used radioimmunoassay to measure serum islet autoantibodies, thyroid autoantibodies and TGA. They found TGA positivity in 22% of patients with either type 1 diabetes or AITD, much higher than the 3.4% seen in T2D patients (p< 0.0001) the 3.1% seen in NAITD patients (P < 0.0001) or the 1% seen in healthy controls (1%; p<0.0001). Thirty-six percent of patients with APS3v who had both T1D and AITD positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). At diagnosis, T1D and AITD showed overlap frequencies of 20% and 30%, respectively. Chinese population with existing T1D and/or AITD shows high rates of TGA positivity, which are even higher in people with both diseases. The study team recommends routine TGA screening in patients with T1D or AITD will help to identify celiac disease autoimmunity early on, and will yield better clinical patient care. Source: Plos.org

Celiac.com 06/13/2016 - Researchers Umberto Volta, Giacomo Caio, and Roberto De Giorgio, of the Department of Medical and Surgical Sciences at the University of Bologna in Bologna, Italy, recently submitted a letter to the medical journal Gastroenterology. In their letter, the researchers respond to a recent paper, published by Carroccio et al, reporting on the prevalence of autoimmunity (as identified by positivity of antinuclear antibodies [ANA] and associated autoimmune disorders) in non-celiac wheat sensitivity (NCWS) compared with celiac disease and irritable bowel syndrome (IBS). They note that the study results, based on retrospective and prospective data, showed that the prevalence of ANA in NCWS was significantly higher than in celiac disease and IBS (46% in NCWS vs 24% in celiac disease and 2% in IBS, retrospectively; and 28% in NCWS vs 7.5% in celiac disease and 6% in IBS, prospectively). They note also that both retrospective and prospective analysis show autoimmune disorders (mainly autoimmune thyroiditis) in a slightly higher proportion in NCWS (29% vs 24%) than celiac disease (21% vs 20%). Meanwhile, both NCWS and celiac patients showed substantially higher rates of autoimmune disorders than IBS. In both both retrospective and prospective data, ANA showed a strong relation to HLA-DQ2 and -DQ8 in NCWS, whereas these autoantibodies were associated with autoimmune disorders only in the prospective arm. The team found these results from the Carroccio study to be scientific interesting because NCWS, more than better known autoimmune disorders, such as celiac disease, shows a surprisingly high autoimmune profile. They note that celiac disease is a well-established autoimmune condition often marked by different types of autoantibodies and associated autoimmune disorders. Such autoimmune features have not been seen so far in NCWS and the odds of these patients developing autoimmune dysfunction remains unknown. The team's data showed that only 14% of 486 patients with NCWS had an associated autoimmune disorder including thyroiditis, psoriasis, Graves disease, type 1 diabetes mellitus, and atrophic gastritis. In contrast, about 30% of 770 celiac patients showed the same autoimmune manifestations. These findings are in line with previously published data. They point out that another interesting aspect that came out of Carroccio study is the very high rate of ANA in their cohort of NCWS versus celiac disease and IBS patients. The team notes that their own experience shows ANA to be higher in celiac disease than NCWS and IBS (49% vs 37% vs 6%), which indicates a substantial autoimmune profile in celiac disease, compared with the two other conditions. They also note that evidence showing patients with NCWS to have higher rates of ANA compared with IBS is in line with the results presented by Carroccio et al. They conclude their letter by stating that consistent evidence supports a major role of adaptive immunity in celiac disease more than NCWS, and this peculiarity is reflected by a predominant occurrence of autoimmune disorders and autoantibodies (eg, ANA). However, the challenging data shown by Carroccio et al provide the basis to understand whether NCWS, like celiac disease, show a wide array of autoimmune expressions mediated by adaptive mechanisms. They call for further studies to better understand what they term the "intriguing relationship between autoimmunity and NCWS." Source: Gastroenterology. 2016 Jan;150(1):282. doi: 10.1053/j.gastro.2015.08.058. Epub 2015 Nov 23.