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Celiac Disease: HELP
Articles from San Diego
Based on 30 articles published since 2010
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These are the 30 published articles about Celiac Disease that originated from San Diego during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Statement on Best Practices in the Use of Pathology as a Diagnostic Tool for Celiac Disease: A Guide for Clinicians and Pathologists. 2018

Robert, Marie E / Crowe, Sheila E / Burgart, Lawrence / Yantiss, Rhonda K / Lebwohl, Benjamin / Greenson, Joel K / Guandalini, Stefano / Murray, Joseph A. ·Rodger C. Haggitt Gastrointestinal Pathology Society (GIPS). · Department of Pathology, Yale University School of Medicine, New Haven, CT. · North American Society for the Study of Celiac Disease (NASSCD). · Division of Gastroenterology, University of California San Diego, San Diego, CA. · Department of Pathology, University of Minnesota, Minneapolis. · Department of Pathology and Laboratory Medicine, Weill Cornell Medicine. · Celiac Disease Center, Columbia University, New York, NY. · Department of Pathology, University of Michigan Hospitals, Ann Arbor, MI. · Section of Pediatric Gastroenterology, University of Chicago, Chicago, IL. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. ·Am J Surg Pathol · Pubmed #29923907.

ABSTRACT: Small intestinal biopsy interpretation has been the cornerstone for the diagnosis of celiac disease for over 50 years. Despite the existence of sensitive and specific serological tests, duodenal mucosal biopsies continue to be obtained in the vast majority of patients in whom a diagnosis of celiac disease is being considered. The accurate evaluation of these biopsies requires coordination and information sharing between the gastroenterologist, laboratory, and pathologist in order to optimize tissue sampling, preparation and interpretation. This document, a collaboration between the Rodger C. Haggitt Gastrointestinal Pathology Society and the North American Association for the Study of Celiac Disease, is intended to provide clinicians and pathologists with a summary of best practices in the use of endoscopy and biopsy for patients with suspected celiac disease. The authors present a comprehensive and critical appraisal of the literature with respect to the topics of endoscopic findings, best methods for the obtaining biopsies, completing the pathology form and pathologic assessment, including evaluating intraepithelial lymphocytes and villous architecture. A discussion of conditions with overlapping pathologic findings in duodenal mucosal biopsies is presented. In order to provide additional guidance for challenging situations, the authors include an appendix containing practical suggestions. This review may be utilized in interdisciplinary discussions to optimize care for patients with possible celiac disease.

2 Guideline Transition from childhood to adulthood in coeliac disease: the Prague consensus report. 2016

Ludvigsson, Jonas F / Agreus, Lars / Ciacci, Carolina / Crowe, Sheila E / Geller, Marilyn G / Green, Peter H R / Hill, Ivor / Hungin, A Pali / Koletzko, Sibylle / Koltai, Tunde / Lundin, Knut E A / Mearin, M Luisa / Murray, Joseph A / Reilly, Norelle / Walker, Marjorie M / Sanders, David S / Shamir, Raanan / Troncone, Riccardo / Husby, Steffen. ·Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Paediatrics, Örebro University Hospital, Örebro, Sweden Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK. · Division of Family Medicine, Karolinska Institutet, Sweden. · Department of Medicine and Surgery, University of Salerno, Salerno, Italy. · University of California, San Diego (UCSD), San Diego, California, USA. · Celiac Disease Foundation, Los Angeles, California, USA. · Celiac Disease Center at Columbia University, New York, New York, USA. · Division of Gastroenterology, Nationwide Children's Hospital, Columbus, Ohio, USA. · Primary Care and General Practice, School of Medicine, Pharmacy and Health, Durham University, Stockton on Tees, UK. · Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany. · Hungary (for the Association of European Coeliac Societies, AOECS), Budapest, Hungary. · Department of Gastroenterology and Centre for Immune Regulation, Oslo University Hospital Rikshospitalet, Oslo, Norway. · Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands. · Division of Gastroenterology and Hepatology, Department of Immunology Mayo Clinic, Rochester, Minnesota, USA. · Columbia University Medical Center-Division of Paediatric Gastroenterology, New York, New York, USA. · Anatomical Pathology, Faculty of Health and Medicine, University of Newcastle, School of Medicine & Public Health, Newcastle, Australia. · Academic Unit of Gastroenterology, Royal Hallamshire Hospital & University of Sheffield, Sheffield, UK. · Institute of Gastroenterology, Nutrition and Liver Diseases Schneider Children's Medical Center of Israel, Tel-Aviv University, Tel Aviv, Israel. · Department of Medical Translational Sciences & European Laboratory for the Investigation of Food Induced Diseases, University Federico II, Naples, Italy. · Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, Denmark. ·Gut · Pubmed #27196596.

ABSTRACT: The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.

3 Editorial Duodenal Bulb Biopsies Remain Relevant in the Diagnosis of Adult Celiac Disease. 2016

Pace, Laura A / Crowe, Sheila E. ·Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, Utah. · Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California. ·Clin Gastroenterol Hepatol · Pubmed #27565522.

ABSTRACT: -- No abstract --

4 Editorial Management of celiac disease: beyond the gluten-free diet. 2014

Crowe, Sheila E. ·Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California. Electronic address: secrowe@ucsd.edu. ·Gastroenterology · Pubmed #24786557.

ABSTRACT: -- No abstract --

5 Review Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet. 2019

Lerner, Aaron / O'Bryan, Thomas / Matthias, Torsten. ·Aesku.KIPP Institute, Wendelsheim, Germany. · Gastroenterology, Clinical Practice and Institute of Functional Medicine, The National University of Health Sciences, San Diego, CA, United States. ·Front Pediatr · Pubmed #31681712.

ABSTRACT: In gluten dependent conditions the gluten free diet is the cornerstone of therapy, decreasing disease activity, improving health and quality of life and treating or preventing the associated complications. Gluten withdrawal implies strict and lifelong elimination not only of wheat, barley, rye, and wheat-contaminated oats, but also of numerous non-nutritional products where components of wheat are often added. Due to multiple reasons the diet is difficult to follow and the long-term adherence is decreased with time. The present review summarizes the dark side of gluten restriction where nutritional deficiencies, toxicity, morbidity, mortality, and mental health problems are reported. The aim being to increase awareness, avoid, detect and treat the side effects and to promote a healthier nutrition, for the patient's benefits.

6 Review Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials. 2018

Hindryckx, Pieter / Levesque, Barrett G / Holvoet, Tom / Durand, Serina / Tang, Ceen-Ming / Parker, Claire / Khanna, Reena / Shackelton, Lisa M / D'Haens, Geert / Sandborn, William J / Feagan, Brian G / Lebwohl, Benjamin / Leffler, Daniel A / Jairath, Vipul. ·Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada. · Department of Gastroenterology, University of Ghent, Ghent, Belgium. · Division of Gastroenterology, University of California San Diego, La Jolla, California, USA. · Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK. · Oxford University Clinical Academic Graduate School, John Radcliffe Hospital, Oxford, UK. · Department of Medicine, University of Western Ontario, London, Ontario, Canada. · Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada. · Celiac Disease Center, Columbia University, New York, New York, USA. · The Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. ·Gut · Pubmed #27799282.

ABSTRACT: OBJECTIVE: Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. DESIGN: MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). RESULTS: Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. CONCLUSIONS: Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.

7 Review Complex Relationships Between Food, Diet, and the Microbiome. 2016

Pace, Laura A / Crowe, Sheila E. ·Division of Gastroenterology, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0063, USA. · Division of Gastroenterology, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0063, USA. Electronic address: secrowe@ucsd.edu. ·Gastroenterol Clin North Am · Pubmed #27261897.

ABSTRACT: Diet is a risk factor in several medically important disease states, including obesity, celiac disease, and functional gastrointestinal disorders. Modification of diet can prevent, treat, or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations to increase the probability of successful implementation. These recommendations include increasing vegetable, fruit, and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients.

8 Review Dietary proteins and functional gastrointestinal disorders. 2013

Boettcher, Erica / Crowe, Sheila E. ·Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA 92093-0063, USA. ·Am J Gastroenterol · Pubmed #23567359.

ABSTRACT: Food intolerance is a common complaint amongst patients with functional gastrointestinal (GI) disorders (FGIDs), including those with irritable bowel syndrome (IBS), functional dyspepsia, as well as gastroesophageal reflux disease. Although there has been a longstanding interest in the possible role of food allergy in IBS, there are limited data supporting the association. However, the prevalence of food allergy is sufficiently high that patients with FGID may also have food allergies or hypersensitivities. Food intolerances or sensitivities are reactions to foods, which are not due to immunological mechanisms. Lactose intolerance is common in the general population and can mimic symptoms of FGID or coexist with FGID. As discussed in other articles in this series, other carbohydrate intolerances may be responsible for symptom generation in patients with IBS and perhaps other FGIDs. There is a great interest in the role of a major dietary protein, gluten, in the production of symptoms that are very similar to those of patients with celiac disease without the enteropathy that characterizes celiac disease. Emerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS. This article summarizes the role of dietary proteins in the symptoms and pathophysiology of FGIDs.

9 Review The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet. 2012

McAllister, Christopher S / Kagnoff, Martin F. ·Department of Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0623D, La Jolla, CA, 92093-0623, USA. csmcallister@ucsd.edu ·Semin Immunopathol · Pubmed #22674144.

ABSTRACT: Celiac disease is a T cell-mediated autoimmune inflammatory disease of the small intestine that is activated by gluten. The diagnosis of celiac disease is challenging as patients display a wide range of symptoms and some are asymptomatic. A lifelong gluten-free diet is the only currently approved treatment of celiac disease. Although the diet is safe and effective, the compliance rates and patient acceptance vary. Furthermore, many patients treated with a gluten-free diet continue to be mildly to severely symptomatic with persistent histological abnormalities, and a small number of patients develop refractory celiac disease. New therapeutic adjuncts and potential alternatives to the gluten-free diet could improve the treatment options for these patients. Advances in understanding the immunopathogenesis of celiac disease have suggested several types of therapeutic strategies that may augment or supplant the gluten-free diet. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to celiac disease-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that reestablish mucosal homeostasis and tolerance to gluten antigens are also being explored. Additionally, it is vital to develop new therapeutic options for refractory celiac disease patients. This review highlights therapeutic strategies that may ultimately improve the health and well-being of individuals with celiac disease.

10 Review Celiac disease in children and adolescents: special considerations. 2012

Newton, Kimberly P / Singer, Shereen A. ·Rady Childrens Hospital, 3020 Children's Way MC5030, San Diego, CA 92123, USA. KPNewton@rchsd.org ·Semin Immunopathol · Pubmed #22549889.

ABSTRACT: Although there are many commonalities between adult and pediatric celiac disease (CD), special considerations must be taken into account when working with children and adolescents. In this patient population, there are unique aspects of the epidemiology, pathogenesis, presentation, diagnosis, and management of CD. In terms of management, early and timely recognition of CD can maximize childhood and adolescent development and prevent complications. This requires insight into the unique presentations of CD in the pediatric population. Furthermore, health care providers must use proper screening methods and continue surveillance of at-risk individuals throughout childhood. Potential interventions for primary prevention of CD in children, although not completely understood, may offer some benefit. The goals of this article are to discuss in detail these special considerations when dealing with pediatric CD.

11 Clinical Trial Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies. 2017

Goel, Gautam / King, Tim / Daveson, A James / Andrews, Jane M / Krishnarajah, Janakan / Krause, Richard / Brown, Gregor J E / Fogel, Ronald / Barish, Charles F / Epstein, Roger / Kinney, Timothy P / Miner, Philip B / Tye-Din, Jason A / Girardin, Adam / Taavela, Juha / Popp, Alina / Sidney, John / Mäki, Markku / Goldstein, Kaela E / Griffin, Patrick H / Wang, Suyue / Dzuris, John L / Williams, Leslie J / Sette, Alessandro / Xavier, Ramnik J / Sollid, Ludvig M / Jabri, Bana / Anderson, Robert P. ·Division of Gastroenterology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA. · Department of Gastroenterology, Auckland City Hospital, Auckland, New Zealand. · School of Medicine, University of Queensland, Brisbane, QLD, Australia. · Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia. · Linear Clinical Research, Nedlands, WA, Australia. · ClinSearch, Chattanooga, TN, USA. · Department of Gastroenterology, Alfred Hospital, Prahran, VIC, Australia. · Clinical Research Institute of Michigan, Chesterfield, MI, USA. · University of North Carolina School of Medicine, Chapel Hill, NC, USA; Wake Gastroenterology and Wake Research Associates, Raleigh, NC, USA. · Atlantic Digestive Specialists, Portsmouth, NH, USA. · Ridgeview Medical Center, Waconia, MN, USA. · Oklahoma Foundation for Digestive Research, Oklahoma City, OK, USA. · Immunology Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; Murdoch Children's Research Institute and Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia. · Immunology Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia. · Tampere Center for Child Health Research and Department of Pediatrics, University of Tampere Faculty of Medicine and Life Sciences and Tampere University Hospital, Tampere, Finland. · Tampere Center for Child Health Research and Department of Pediatrics, University of Tampere Faculty of Medicine and Life Sciences and Tampere University Hospital, Tampere, Finland; Alfred Rusescu Institute for Mother and Child Care and Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. · Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. · ImmusanT, Cambridge, MA, USA. · Centre for Immune Regulation, KG Jebsen Coeliac Disease Research Centre, and Department of Immunology, University of Oslo, Oslo, Norway; Oslo University Hospital-Rikshospitalet, Oslo, Norway. · Department of Pediatrics, Department of Medicine, University of Chicago, Chicago, IL, USA. · ImmusanT, Cambridge, MA, USA. Electronic address: bob@immusant.com. ·Lancet Gastroenterol Hepatol · Pubmed #28506538.

ABSTRACT: BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet. METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18-70 years who had coeliac disease and were on a gluten-free diet. In the screening period for ascending dose cohorts, participants were randomly assigned (1:1) by central randomisation with a simple block method to a double-blind crossover, placebo-controlled oral gluten challenge. Participants with a negative interferon γ release assay to Nexvax2 peptides after the screening oral gluten challenge were discontinued before dosing. For the biopsy cohorts, the screening period included an endoscopy, and participants with duodenal histology who had a Marsh score of greater than 1 were discontinued before dosing. Participants were subsequently randomly assigned to either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts (1:1) by central randomisation with a simple block method. In the three-dose study, participants received either Nexvax2 60 μg, 90 μg, or 150 μg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or placebo. In the 16-dose study, participants received Nexvax2 150 μg or 300 μg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent a further double-blind crossover, placebo-controlled oral gluten challenge, which had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies and quantitative histology within 2 weeks without oral gluten challenge. Participants, investigators, and study staff were masked to the treatment assignment, except for the study pharmacist. The primary endpoint was the number and percentage of adverse events in the treatment period in an intention-to-treat analysis. Both trials were completed and closed before data analysis. Trials were registered with the Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729. FINDINGS: Participants were enrolled from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3, 2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108 participants were randomly assigned after oral gluten challenge and 20 (71%) of 28 participants were randomly assigned after endoscopy. In the three-dose study, nine participants were randomly allocated to Nexvax2 60 μg and three to placebo (first cohort), nine were allocated to Nexvax2 90 μg and four to placebo (second cohort), eight were allocated to Nexvax2 150 μg and four to placebo (third cohort), and three were allocated to Nexvax2 150 μg and three to placebo (biopsy cohort). In the 16-dose study, eight participants were randomly allocated to Nexvax2 150 μg and four to placebo (first cohort), ten were allocated to Nexvax2 300 μg and three to placebo (second cohort), and seven were allocated to Nexvax2 150 μg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 μg because of transient, acute gastrointestinal adverse events with onset 2-5 h after initial doses of the vaccine, similar to those caused by gluten ingestion. In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo recipients, five (56%) of nine who received Nexvax2 60 μg, seven (78%) of nine who received Nexvax2 90 μg, and five (63%) of eight who received Nexvax2 150 μg had at least one treatment-emergent adverse event, as did all three (100%) placebo recipients and one (33%) of three Nexvax2 150 μg recipients in the biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of seven placebo-treated participants, six (75%) of eight who received Nexvax2 150 μg, and all ten (100%) who received Nexvax2 300 μg had at least one treatment-emergent adverse event, as did six (86%) of seven placebo recipients and five (71%) of seven Nexvax2 150 μg recipients in the biopsy cohort. Vomiting, nausea, and headache were the only treatment-emergent adverse events that occurred in at least 5% of participants in either study. Among participants given the MTD, eight gastrointestinal treatment-emergent adverse events occurred in four (50%) of eight participants in the third cohort and none (0%) of three participants in the biopsy cohort in the three-dose study, and five events occurred in five (63%) of eight participants in the first cohort and three events in two (29%) of seven participants in the biopsy cohort of the 16-dose study. Median villous height to crypt depth ratio in distal duodenal biopsies was not significantly different between those who received the vaccine at the MTD on either schedule and those who received placebo. Of the participants who completed the post-treatment oral gluten challenge per protocol, interferon γ release assay to Nexvax2 peptides was negative (responders to treatment) in two (22%) of nine placebo-treated participants in the three-dose study versus two (33%) of six who received Nexvax2 60 μg, five (63%) of eight who received Nexvax2 90 μg, and six (100%) of six who received Nexvax2 150 μg (p=0·007); in the 16-dose study, none (0%) of five placebo-treated participants had a negative assay versus six (75%) of eight who received Nexvax2 150 μg (p=0·021). INTERPRETATION: The MTD of Nexvax2 was 150 μg for twice weekly intradermal administration over 8 weeks, which modified immune responsiveness to Nexvax2 peptides without deterioration in duodenal histology. The gastrointestinal symptoms that followed the first intradermal administration of the vaccine resembled those associated with oral gluten challenge. These findings support continued clinical development of this potential therapeutic vaccine for coeliac disease. FUNDING: ImmusanT.

12 Article Comparison of celiac disease markers in women with early recurrent pregnancy loss and normal controls. 2019

Kutteh, Michael A / Abiad, May / Norman, Gary L / Kutteh, William H. ·University of Oklahoma College of Medicine, Oklahoma City, Oklahoma. · American University of Beirut School of Medicine, Beirut, Lebanon. · INOVA Diagnostics, Inc, San Diego, California. · Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Fertility Associates of Memphis, Memphis, Tennessee. ·Am J Reprod Immunol · Pubmed #30977932.

ABSTRACT: PROBLEM: Celiac disease (CD) is an autoimmune intestinal inflammatory disease triggered by gluten in the diet. Untreated CD has been associated with pregnancy loss and infertility. The purpose of this study was to screen unselected women with recurrent pregnancy loss (RPL) for markers of CD to determine whether a correlation exists between RPL and CD serum markers. METHOD OF STUDY: Frequencies of three serum markers of CD [tissue transglutaminase (TTG) IgA, endomysial (EMA) IgA, and deaminated gliadin peptide (DGP) IgA] were determined by enzyme-linked immunoassay (ELISA). Seven hundred and eight women who had two or more failed clinical pregnancies (cases) and one hundred women with at least one live birth and no miscarriages (controls) were included in this study. All cases had a full workup for RPL based on the American Society for Reproductive Medicine 2013 guidelines. Antiphospholipid antibodies (aPL) were correlated with CD markers based on their potential prothrombotic role. Results The results show no significant difference in the prevalence of CD autoantibodies when comparing the RPL patients with the controls. Over half of the patients who tested positive for serum markers for CD also had positive aPL. Conclusion Screening unselected women with RPL who are asymptomatic for CD is not supported based on these data. Women who test positive for CD may be candidates for aPL testing based on the association of adverse pregnancy outcomes.

13 Article Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. 2019

Caminero, Alberto / McCarville, Justin L / Galipeau, Heather J / Deraison, Celine / Bernier, Steve P / Constante, Marco / Rolland, Corinne / Meisel, Marlies / Murray, Joseph A / Yu, Xuechen B / Alaedini, Armin / Coombes, Brian K / Bercik, Premysl / Southward, Carolyn M / Ruf, Wolfram / Jabri, Bana / Chirdo, Fernando G / Casqueiro, Javier / Surette, Michael G / Vergnolle, Nathalie / Verdu, Elena F. ·Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, L8S 4K1, ON, Canada. · IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, 31300, France. · Department of Medicine, University of Chicago, Chicago, 60637, IL, USA. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, PA, USA. · Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic College of Medicine, Rochester, 55905, MN, USA. · Department of Medicine, Columbia University, New York, 10032, NY, USA. · Celiac Disease Center, Columbia University, New York, 10032, NY, USA. · Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, L8S 4K1, ON, Canada. · Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, Mainz, 55131, Germany. · Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, 92037, CA, USA. · Instituto de Estudios Inmunologicos y Fisiopatologicos - IIFP (UNLP-CONICET). Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, 1900, Argentina. · Department of Microbiology, Universidad de Leon, Leon, 24071, Spain. · Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, L8S 4K1, ON, Canada. verdue@mcmaster.ca. ·Nat Commun · Pubmed #30867416.

ABSTRACT: Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the underlying mechanisms are incompletely understood. Here we show that duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten substrates that correlates with increased Proteobacteria abundance, including Pseudomonas. Using Pseudomonas aeruginosa producing elastase as a model, we show gluten-independent, PAR-2 mediated upregulation of inflammatory pathways in C57BL/6 mice without villus blunting. In mice expressing CeD risk genes, P. aeruginosa elastase synergizes with gluten to induce more severe inflammation that is associated with moderate villus blunting. These results demonstrate that proteases expressed by opportunistic pathogens impact host immune responses that are relevant to the development of food sensitivities, independently of the trigger antigen.

14 Article An integrated, accurate, rapid, and economical handheld consumer gluten detector. 2019

Zhang, Jingqing / Portela, Steven Barbosa / Horrell, Joseph Benjamin / Leung, Alex / Weitmann, Dane Rene / Artiuch, John Boguslaw / Wilson, Stephen Michael / Cipriani, Monica / Slakey, Lyndsie Katherine / Burt, Aquanette Michele / Dias Lourenco, Francisco Javier / Spinali, Marc Stephen / Ward, Jonathan Robert / Seit-Nebi, Alim / Sundvor, Scott Erik / Yates, Shireen Natasha. ·Nima Labs, Inc., 450 Alabama St., San Francisco, CA 94110, United States. Electronic address: jingqing@nimasensor.com. · Nima Labs, Inc., 450 Alabama St., San Francisco, CA 94110, United States. · GenWay Biotech, Inc., 6777 Nancy Ridge Drive, San Diego, CA 92121, United States. ·Food Chem · Pubmed #30724219.

ABSTRACT: Celiac disease, characterized by autoimmune reactions to dietary gluten, affects up to 3 million in the US and approximately 0.5%-1% globally. A strict, lifelong gluten-free diet is the only treatment. An economic, simple, accurate, rapid and portable gluten testing device would enable gluten-sensitive individuals to safeguard their food safety. We developed a novel solution, Nima™, a gluten sensor that integrates food processing, gluten detection, result interpretation and data transmission in a portable device, detecting gluten proteins at or below the accepted 20 ppm threshold. We developed specific monoclonal antibodies, an optimized lateral flow immunoassay strip, and one-step aqueous extraction. Compared with reference R5, Nima

15 Article Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. 2018

Tylee, Daniel S / Sun, Jiayin / Hess, Jonathan L / Tahir, Muhammad A / Sharma, Esha / Malik, Rainer / Worrall, Bradford B / Levine, Andrew J / Martinson, Jeremy J / Nejentsev, Sergey / Speed, Doug / Fischer, Annegret / Mick, Eric / Walker, Brian R / Crawford, Andrew / Grant, Struan F A / Polychronakos, Constantin / Bradfield, Jonathan P / Sleiman, Patrick M A / Hakonarson, Hakon / Ellinghaus, Eva / Elder, James T / Tsoi, Lam C / Trembath, Richard C / Barker, Jonathan N / Franke, Andre / Dehghan, Abbas / Anonymous6591115 / Anonymous6601115 / Anonymous6611115 / Anonymous6621115 / Anonymous6631115 / Anonymous6641115 / Faraone, Stephen V / Glatt, Stephen J. ·Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York. · Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University (LMU), Munich, Germany. · Departments of Neurology and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia. · Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. · Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. · Department of Medicine, University of Cambridge, Cambridge, United Kingdom. · Genetics Institute, University College London, WC1E 6BT, London, United Kingdom. · Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. · Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts. · BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom. · School of Social and Community Medicine, MRC Integrated Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom. · Center for Applied Genomics, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. · Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. · Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Endocrine Genetics Laboratory, Department of Pediatrics and the Child Health Program of the Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. · Quantinuum Research LLC, San Diego, California. · Department of Dermatology, Veterans Affairs Hospital, University of Michigan, Ann Arbor, Michigan. · Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. · Division of Genetics and Molecular Medicine, King's College London, London, UK. · Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health School of Public Health, Imperial College London, London, United Kingdom. · 23andMe, Inc., Mountain View, California. · K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. ·Am J Med Genet B Neuropsychiatr Genet · Pubmed #30325587.

ABSTRACT: Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

16 Article Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases. 2017

Witoelar, Aree / Jansen, Iris E / Wang, Yunpeng / Desikan, Rahul S / Gibbs, J Raphael / Blauwendraat, Cornelis / Thompson, Wesley K / Hernandez, Dena G / Djurovic, Srdjan / Schork, Andrew J / Bettella, Francesco / Ellinghaus, David / Franke, Andre / Lie, Benedicte A / McEvoy, Linda K / Karlsen, Tom H / Lesage, Suzanne / Morris, Huw R / Brice, Alexis / Wood, Nicholas W / Heutink, Peter / Hardy, John / Singleton, Andrew B / Dale, Anders M / Gasser, Thomas / Andreassen, Ole A / Sharma, Manu / Anonymous1261133. ·Norwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo2Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Department of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands4German Center for Neurodegenerative Diseases (DZNE), Tübingen. · Norwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo5Multimodal Imaging Laboratory, University of California at San Diego, La Jolla. · Multimodal Imaging Laboratory, University of California at San Diego, La Jolla6Department of Radiology and Biomedical Imaging, University of California, San Francisco. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland. · German Center for Neurodegenerative Diseases (DZNE), Tübingen. · Department of Psychiatry, University of California at San Diego, La Jolla9Department of Psychiatry, University of Copenhagen, Copenhagen, Denmark. · Norwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo10Department of Medical Genetics, University of Oslo, Oslo, Norway11Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. · Multimodal Imaging Laboratory, University of California at San Diego, La Jolla12Sciences Graduate Program, University of California at San Diego, La Jolla13Department of Neurosciences, University of California at San Diego, La Jolla. · Norwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo. · Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. · Department of Medical Genetics, University of Oslo, Oslo, Norway11Department of Medical Genetics, Oslo University Hospital, Oslo, Norway15K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway16Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway17Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. · Multimodal Imaging Laboratory, University of California at San Diego, La Jolla15K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway. · K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway16Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway18Division of Gastroenterology, Institute of Medicine, University of Bergen, Bergen, Norway19Norwegian Primary Sclerosing Cholangitis (PSC) Research Center, Department of Transplantation Medicine, Oslo. · Sorbonne Universités, Université Pierre-et-Marie Curie (UPMC) Paris 06, UM 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France21Institut National de la Santé et de la Récherche Médicale (INSERM), Unité 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France22Centre National de la Recherche Scientifique (CNRS) UMR 7225, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France23Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France24Assistance Publique-Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France. · Department of Clinical Neuroscience, National Hospital for Neurology and Neurosurgery (NHNN), University College London, London, England. · Department of Molecular Neurosciences, Institute of Neurology, University College London, London, England. · Department of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands4German Center for Neurodegenerative Diseases (DZNE), Tübingen27Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. · Rita Lila Weston Institute, University College London, London, England. · Multimodal Imaging Laboratory, University of California at San Diego, La Jolla8Department of Psychiatry, University of California at San Diego, La Jolla13Department of Neurosciences, University of California at San Diego, La Jolla29Department of Radiology, University of California at San Diego, La Jolla. · German Center for Neurodegenerative Diseases (DZNE), Tübingen27Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. · Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany30Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. ·JAMA Neurol · Pubmed #28586827.

ABSTRACT: Importance: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Design, Setting, and Participants: Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. Main Outcomes and Measures: The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Results: Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. Conclusions and Relevance: The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.

17 Article Gliadin-Specific CD8 2017

Picascia, Stefania / Sidney, John / Camarca, Alessandra / Mazzarella, Giuseppe / Giardullo, Nicola / Greco, Luigi / Auricchio, Renata / Auricchio, Salvatore / Troncone, Riccardo / Sette, Alessandro / Gianfrani, Carmen. ·Institute of Protein Biochemistry-National Research Council, 80131 Naples, Italy. · La Jolla Institute for Allergy and Immunology, La Jolla, CA 92130. · Institute of Food Sciences-National Research Council, 83100 Avellino, Italy. · Department of Translational Medical Science and European Laboratory for Investigation and Food-Induced Diseases, University Federico II, 80131 Naples, Italy; and. · Gastroenterology Unit, Hospital Moscati, 83100 Avellino, Italy. · Institute of Protein Biochemistry-National Research Council, 80131 Naples, Italy; c.gianfrani@ibp.cnr.it. ·J Immunol · Pubmed #28148736.

ABSTRACT: Initial studies associated the HLA class I A*01 and B*08 alleles with celiac disease (CD) susceptibility. Subsequent analyses showed a primary association with HLA class II alleles encoding for the HLA DQ2.5 molecule. Because of the strong linkage disequilibrium of A*01 and B*08 alleles with the DR3-DQ2.5 haplotype and a recent genome-wide association study indicating that B*08 and B*39 are predisposing genes, the etiologic role of HLA class I in CD pathogenesis needs to be addressed. We screened gliadin proteins (2α-, 2ω-, and 2γ-gliadin) using bioinformatic algorithms for the presence of peptides predicted to bind A*0101 and B*0801 molecules. The top 1% scoring 9- and 10-mer peptides (

18 Article Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children. 2016

Snyder, John / Butzner, J Decker / DeFelice, Amy R / Fasano, Alessio / Guandalini, Stefano / Liu, Edwin / Newton, Kimberly P. ·Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's National Health Systems, Washington, District of Columbia; butzner@ucalgary.ca. · Division of Paediatric Gastroenterology, Hepatology and Nutrition, University of Calgary, Calgary, Alberta, Canada; · Division of Pediatric Gastroenterology, Hepatology and Nutrition, New York-Presbyterian Hospital, Columbia University, New York, New York; · Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital for Children, Boston, Massachusetts; · Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Medical Center, Chicago, Illinois; · Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado; and. · Division of Pediatric Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital and University of California San Diego School of Medicine, San Diego, California. ·Pediatrics · Pubmed #27565547.

ABSTRACT: Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.

19 Article Gluten Introduction, Breastfeeding, and Celiac Disease: Back to the Drawing Board. 2016

Lebwohl, Benjamin / Murray, Joseph A / Verdú, Elena F / Crowe, Sheila E / Dennis, Melinda / Fasano, Alessio / Green, Peter H R / Guandalini, Stefano / Khosla, Chaitan. ·Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York, New York, USA. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Gastroenterology, Department of Medicine, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. · Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA. · Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. · Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, Boston, Massachusetts, USA. · Pediatric Gastroenterology, Hepatology and Nutrition, Celiac Disease Center, University of Chicago, Chicago, Illinois, USA. · School of Engineering, Department of Chemistry, Stanford University, Stanford, California, USA. ·Am J Gastroenterol · Pubmed #26259710.

ABSTRACT: This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies.

20 Article Low yield of routine duodenal biopsies for evaluation of abdominal pain. 2015

Dubin, Sterling M / Kwong, Wilson T / Kalmaz, Denise / Savides, Thomas J. ·Sterling M Dubin, Wilson T Kwong, Denise Kalmaz, Thomas J Savides, Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, CA 92093-0956, United States. ·World J Gastroenterol · Pubmed #26139995.

ABSTRACT: AIM: To determine the yield of biopsying normal duodenal mucosa for investigation of abdominal pain. METHODS: This is a retrospective chart review of consecutive patients who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsies of normal appearing duodenal mucosa for an indication that included abdominal pain. All the patients in this study were identified from an electronic endoscopy database at a single academic medical center and had an EGD with duodenal biopsies performed over a 4-year period. New diagnoses that were made as a direct result of duodenal biopsies were identified. All duodenal pathology reports and endoscopy records were reviewed for indications to perform the examination as well as the findings; all the medical records were reviewed. Exclusion criteria included age less than 18 years, duodenal mass, nodule, or polyp, endoscopic duodenitis, duodenal scalloping, known celiac disease, positive celiac serology, Crohns disease, or history of bone marrow transplant. Information was collected in a de-identified database with pertinent demographic information including human immunodeficiency virus (HIV) status, and descriptive statistics were performed. RESULTS: About 300 patients underwent EGD with biopsies of benign appearing or normal appearing duodenal mucosa. The mean age of patients was 44.1 ± 16.8 years; 189 of 300 (63%) were female. A mean of 4.3 duodenal biopsies were performed in each patient. In the subgroup of patients with abdominal pain without anemia, diarrhea, or weight loss the mean age was 43.4 ± 16.3 years. Duodenal biopsies performed for an indication that included abdominal pain resulting in 4 new diagnoses (3 celiac disease and 1 giardiasis) for an overall yield of 1.3%. 183 patients with abdominal pain without anemia, diarrhea, or weight loss (out of the total 300 patients) underwent duodenal biopsy of duodenal mucosa resulting in three new diagnoses (two cases of celiac disease and one giardiasis) for a yield of 1.6%. Duodenal biopsies of 19 HIV patients presenting for evaluation of abdominal pain did not reveal any new diagnoses. Information pertaining to new diagnoses is provided. CONCLUSION: Routine biopsy of normal appearing duodena in patients with abdominal pain should be reserved for those with a high pre-test probability given its low diagnostic yield.

21 Article Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping. 2015

Leja, Marcis / Shums, Zakera / Nikitina-Zake, Liene / Gavars, Mikus / Kikuste, Ilze / Milo, Jay / Daugule, Ilva / Pahomova, Jelena / Pirags, Valdis / Dzerve, Vilnis / Klovins, Janis / Erglis, Andrejs / Norman, Gary L. ·University of Latvia, Faculty of Medicine, Riga East University Hospital, Riga, Latvia. · Inova Diagnostics Inc, San Diego, CA, USA. · Latvian Biomedical Research and Study Centre, Riga, Latvia. · University of Latvia, Riga, Latvia. · Institute of Cardiology, University of Latvia, Riga, Latvia. · University of Latvia, Faculty of Medicine, Pauls Stradins Clinical University Hospital, Riga, Latvia. ·United European Gastroenterol J · Pubmed #25922680.

ABSTRACT: BACKGROUND: Prevalence estimates for celiac disease (CD) depend on the method used. The role of deamidated gliadin peptide (DGP) and genetic testing in epidemiological studies and diagnostic settings of celiac disease (CD) has still to be established. OBJECTIVES: The objective of this article is to assess the prevalence of CD in Latvia by combining serological tests with DQ2.5/DQ8 testing. METHODS: A total of 1444 adults from a randomly selected cross-sectional general population sample were tested by ELISA for tTG IgA, DGP IgA and IgG antibodies (QUANTA Lite®, Inova Diagnostics Inc). Samples with tTG IgA ≥20U were tested for EMA IgA by indirect immunofluorescence assay, and all specimens with tTG IgA ≥15U were tested by QUANTA-Flash® chemiluminescent assays (CIA) (Inova Diagnostics Inc) for tTG IgA, DGP IgA and IgG. DQ2.5/8 was detected in individuals with any positive ELISA test and a subgroup of controls. RESULTS: Forty-three individuals (2.98%; 95% CI: 2.10-3.86%) tested positive by at least one ELISA test; 41.86% of the serology-positive individuals (any test above the cutoff) were DQ positive. Six individuals (0.42%; 95% CI: 0.09-0.75%) were triple ELISA positive, and DQ2.5 or DQ8 was positive in all; 0.35% (95% CI: 0.05-0.65%) were tTG IgA and EMA positive. Two tTG IgA-negative cases were both DGP IgG and IgA positive, both being DQ positive; including them in the "serology-positive" group would increase the prevalence to 0.49% (95% CI: 0.13-0.85%). CIA tests revealed 2 tTG IgA-positive and EMA-negative cases with a positive genotype. DQ2.5 or DQ8 genotype was positive in 28.6% of the serology-negative population. CONCLUSIONS: Estimates of the prevalence of CD in Latvia based on the serogenetic testing approach range from 0.35% to 0.49% depending on the criteria used. There is a rationale for combining serological tests and DQ2.5/8 genotyping.

22 Article Analytical and clinical comparison of two fully automated immunoassay systems for the diagnosis of celiac disease. 2014

Lakos, Gabriella / Norman, Gary L / Mahler, Michael / Martis, Peter / Bentow, Chelsea / Santora, Debby / Fasano, Alessio. ·INOVA Diagnostics, Inc., 9900 Old Grove Road, San Diego, CA 92131-1638, USA. · University of Maryland, Baltimore, MD 21201, USA. · Center for Celiac Research, Massachusetts Hospital for Children, Boston, MA 02114, USA. ·J Immunol Res · Pubmed #24741592.

ABSTRACT: OBJECTIVE: Here we compared analytical and clinical performance characteristics of two novel automated assay systems for the detection of celiac disease (CD) specific antibodies: QUANTA Flash (INOVA Diagnostics, Inc.) and EliA (Thermo Scientific). METHODS: A total of 74 biopsy-proven CD patients (2 with IgA deficiency) and 138 controls were tested by both methods. RESULTS: Sensitivities of QUANTA Flash assays ranged from 35.1% to 90.5% and specificities from 96.4% to 99.3%, while sensitivities for EliA assays ranged from 37.8% to 90.5% (equivocal considered positive) and specificities from 97.1% to 100.0%. Good qualitative agreement was found between all assays. Thirty-four (50.0%) of the 68 QUANTA Flash h-tTG IgA positive results were higher than 10 times the upper limit of normal (ULN). In contrast, only 22.8% of the EliA tTG IgA positive samples were >10x ULN. Seventy-three (98.6%) biopsy-proven CD patients were correctly identified with the QUANTA Flash h-tTG IgA+DGP IgG combination, while 64 (86.5%) and 72 (97.3%) (depending on equivocal range) were identified with the same combination of EliA assays. CONCLUSION: The QUANTA Flash CD assays have outstanding clinical performance. Of particular clinical significance, in light of proposals to decrease the absolute necessity of biopsy, was the demonstration that 50% of the QUANTA Flash h-tTG IgA results were >10x ULN.

23 Article Barriers impeding serologic screening for celiac disease in clinically high-prevalence populations. 2014

Barbero, Erika M / McNally, Shawna L / Donohue, Michael C / Kagnoff, Martin F. ·Department of Medicine, Division of Gastroenterology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 MC 0623D, USA. mkagnoff@ucsd.edu. ·BMC Gastroenterol · Pubmed #24592899.

ABSTRACT: BACKGROUND: Celiac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease. METHODS: 119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test. RESULTS: Two barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co-morbid conditions were similar among those whose IgA tTG were negative and those who tested positive. CONCLUSION: There are significant patient-centered barriers that impede serologic screening and contribute to the delayed detection and diagnosis of celiac disease. These barriers may be lessened by greater education of the public and health care professionals about celiac disease symptoms, risk factors, and serologic testing.

24 Article Identifying common genetic variants in blood pressure due to polygenic pleiotropy with associated phenotypes. 2014

Andreassen, Ole A / McEvoy, Linda K / Thompson, Wesley K / Wang, Yunpeng / Reppe, Sjur / Schork, Andrew J / Zuber, Verena / Barrett-Connor, Elizabeth / Gautvik, Kaare / Aukrust, Pål / Karlsen, Tom H / Djurovic, Srdjan / Desikan, Rahul S / Dale, Anders M / Anonymous4390780. ·Department of Radiology, University of California, San Diego, 8950 Villa La Jolla Dr, Suite C101, La Jolla, CA 92037-0841. amdale@ucsd.edu; and Ole A. Andreassen, NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, 0424 Oslo, Norway. Email o.a.andreassen@medisin.uio.no. ·Hypertension · Pubmed #24396023.

ABSTRACT: Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP.

25 Article Can consumers trust web-based information about celiac disease? Accuracy, comprehensiveness, transparency, and readability of information on the internet. 2012

McNally, Shawna L / Donohue, Michael C / Newton, Kimberly P / Ogletree, Sandra P / Conner, Kristen K / Ingegneri, Sarah E / Kagnoff, Martin F. ·Wm. K. Warren Medical Research Center for Celiac Disease, Department of Medicine, University of California, San Diego, La Jolla, CA, United States. ·Interact J Med Res · Pubmed #23611901.

ABSTRACT: BACKGROUND: Celiac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content. OBJECTIVES: To determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease. METHODS: Using the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality. RESULTS: We included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of 98 (52%) websites contained less than 50% of the core celiac disease information that was considered important for inclusion on websites that provide general information about celiac disease. Academic websites were significantly less transparent (P = .005) than commercial websites in attributing authorship, timeliness of information, sources of information, and other important disclosures. The type of website publisher did not predict website accuracy, comprehensiveness, or overall website quality. Only 4 of 98 (4%) websites achieved an overall quality score of 80 or above, which a priori was set as the minimum score for a website to be judged trustworthy and reliable. CONCLUSIONS: The information on many websites addressing celiac disease was not sufficiently accurate, comprehensive, and transparent, or presented at an appropriate reading grade level, to be considered sufficiently trustworthy and reliable for patients, health care providers, celiac disease support groups, and the general public. This has the potential to adversely affect decision making about important aspects of celiac disease, including its appropriate and proper diagnosis, treatment, and management.

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