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Celiac Disease: HELP
Articles from Washington
Based on 32 articles published since 2010
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These are the 32 published articles about Celiac Disease that originated from Washington during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Screening for Celiac Disease: US Preventive Services Task Force Recommendation Statement. 2017

Anonymous3260901 / Bibbins-Domingo, Kirsten / Grossman, David C / Curry, Susan J / Barry, Michael J / Davidson, Karina W / Doubeni, Chyke A / Ebell, Mark / Epling, John W / Herzstein, Jessica / Kemper, Alex R / Krist, Alex H / Kurth, Ann E / Landefeld, C Seth / Mangione, Carol M / Phipps, Maureen G / Silverstein, Michael / Simon, Melissa A / Tseng, Chien-Wen. ·University of California, San Francisco. · Group Health Research Institute, Seattle, Washington. · University of Iowa, Iowa City. · Harvard Medical School, Boston, Massachusetts. · Columbia University, New York, New York. · University of Pennsylvania, Philadelphia. · University of Georgia, Athens. · Virginia Tech Carilion School of Medicine, Roanoke. · Independent consultant, Washington, DC. · Duke University, Durham, North Carolina. · Fairfax Family Practice Residency, Fairfax, Virginia12Virginia Commonwealth University, Richmond. · Yale University, New Haven, Connecticut. · University of Alabama at Birmingham. · University of California, Los Angeles. · Brown University, Providence, Rhode Island. · Boston University, Boston, Massachusetts. · Northwestern University, Evanston, Illinois. · University of Hawaii, Manoa. ·JAMA · Pubmed #28350936.

ABSTRACT: Importance: Celiac disease is caused by an immune response in persons who are genetically susceptible to dietary gluten, a protein complex found in wheat, rye, and barley. Ingestion of gluten by persons with celiac disease causes immune-mediated inflammatory damage to the small intestine. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for celiac disease. Evidence Review: The USPSTF reviewed the evidence on the accuracy of screening in asymptomatic adults, adolescents, and children; the potential benefits and harms of screening vs not screening and targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease. The USPSTF also reviewed contextual information on the prevalence of celiac disease among patients without obvious symptoms and the natural history of subclinical celiac disease. Findings: The USPSTF found inadequate evidence on the accuracy of screening for celiac disease, the potential benefits and harms of screening vs not screening or targeted vs universal screening, and the potential benefits and harms of treatment of screen-detected celiac disease. Conclusions and Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. (I statement).

2 Review Gluten Detection Methods and Their Critical Role in Assuring Safe Diets for Celiac Patients. 2019

Osorio, Claudia E / Mejías, Jaime H / Rustgi, Sachin. ·Agriaquaculture Nutritional Genomic Center, CGNA, Las Heras 350, Temuco 4781158, Chile. · Centro Regional de Investigación Carillanca, Instituto de Investigaciones Agropecuarias INIA, Temuco 4880000, Chile. · Department of Crop and Soil Sciences, Washington State University, Pullman, WA 99164, USA. · Department of Plant and Environmental Sciences, School of Health Research, Clemson University Pee Dee Research and Education Center, Florence, SC 29506, USA. ·Nutrients · Pubmed #31810336.

ABSTRACT: Celiac disease, wheat sensitivity, and allergy represent three different reactions, which may occur in genetically predisposed individuals on the ingestion of wheat and derived products with various manifestations. Improvements in the disease diagnostics and understanding of disease etiology unveiled that these disorders are widespread around the globe affecting about 7% of the population. The only known treatment so far is a life-long gluten-free diet, which is almost impossible to follow because of the contamination of allegedly "gluten-free" products. Accidental contamination of inherently gluten-free products could take place at any level from field to shelf because of the ubiquity of these proteins/grains. Gluten contamination of allegedly "gluten-free" products is a constant threat to celiac patients and a major health concern. Several detection procedures have been proposed to determine the level of contamination in products for celiac patients. The present article aims to review the advantages and disadvantages of different gluten detection methods, with emphasis on the recent technology that allows identification of the immunogenic-gluten peptides without the use of antibodies. The possibility to detect gluten contamination by different approaches with similar or better detection efficiency in different raw and processed foods will guarantee the safety of the foods for celiac patients.

3 Review Systematic review: patient-reported outcome measures in coeliac disease for regulatory submissions. 2016

Canestaro, W J / Edwards, T C / Patrick, D L. ·Pharmaceutical Outcomes Research and Policy Program, University of Washington School of Pharmacy, Seattle, WA, USA. · Department of Health Services, Seattle Quality of Life Group, University of Washington School of Public Health, Seattle, WA, USA. ·Aliment Pharmacol Ther · Pubmed #27349458.

ABSTRACT: BACKGROUND: New therapeutics are moving into phase 3 clinical trials for the treatment of coeliac disease, a condition with no established therapies other than gluten-free diet. These trials will require a meaningful, validated and fit for purpose patient-reported outcome measure (PROM) to quantify the symptomatic improvement of patients. AIM: To evaluate existing PROMs for suitability in a Food and Drug Administration (FDA) approval trial for a coeliac disease therapeutic. METHOD: We performed a systematic search in five online databases (MedLine, EmBase, Web of Science, CENTRAL, CINAHL) for studies that enrolled patients with coeliac disease and used PROMs. Studies included in this review had to measure some PROM concept, be patient administered and based upon a previously validated instrument with published measurement properties. RESULTS: Our literature search identified 2706 unique records of which 199 ultimately qualified for abstraction. The majority of PROMs used in studies of coeliac disease was generic and did not measure numerous symptoms or concerns of interest to patients. Four PROMs were found to contain appropriate content for use in an FDA trial: the coeliac disease-specific modification of the Gastrointestinal Symptoms Rating Scale (CeD-GSRS), Psychological General Well-Being Index (PGWB), the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient Reported Outcome (CeD-PRO). The GSRS and PGWB are most often used together and are two of the most extensively used measures in coeliac disease. The CDSD and CeD-PRO were developed exclusively for trials in coeliac disease but have much less published information on their measurement properties. CONCLUSIONS: While we did not find PROMs that currently meet the stated expectations of the FDA for regulatory purposes, four PROMs (CeD-GSRS, PGWB, CDSD and CeD-PRO) appear to contain appropriate content and with modest additional validation work could meet scientific standards for valid and sensitive measures of disease and treatment outcome. Specifically, what is needed for these instruments is an understanding of how sensitive they are to real changes in-patient condition, how stable they are over a period of time when health status should not have changed (test-retest reliability) as well as how they correlate with other measures of patient functioning such as intestinal biopsy. All of these objectives could feasibly be accomplished over a short cohort study of patients with biopsy-defined coeliac disease undergoing gluten challenge.

4 Review Targeted modification of wheat grain protein to reduce the content of celiac causing epitopes. 2012

Osorio, C / Wen, N / Gemini, R / Zemetra, R / von Wettstein, D / Rustgi, S. ·Department of Crop & Soil Sciences, Washington State University, Pullman, WA 99164, USA. ·Funct Integr Genomics · Pubmed #22732824.

ABSTRACT: The prolamin peptides in wheat gluten and in the homologous storage proteins of barley and rye cause painful chronic erasure of microvilli of the small intestine epithelium in celiac patients. If untreated, it can lead to chronic diarrhea, abdominal distension, osteoporosis, weight-loss due to malabsorption of nutrients, and anemia. In addition to congenital cases, life-long exposure to gluten proteins in bread and pasta can also induce development of celiac sprue in adults. To date, the only effective treatment is life-long strict abstinence from the staple food grains. Complete exclusion of dietary gluten is, however, difficult due to use of wheat in many foods, incomplete labeling and social constraints. Thus, finding alternative therapies for this most common foodborne disease remained an active area of research, which has led to many suggestions in last few years. The pros and cons associated with these therapies were reviewed in the present communication. As different celiac patients are immunogenic to different members of the undigestible proline/glutamine rich peptides of ~149 gliadins and low molecular weight glutenin subunits as well as the six high molecular weight glutenin subunits, an exhaustive digestion of the immunogenic peptides in the stomach, duodenum, jejunum, and ileum of celiacs is required. In view of the above, we evaluated the capacity of cereal grains to synthesize and store the enzymes prolyl endopeptidase from Flavobacterium meningosepticum and the barley cysteine endoprotease B2, which in combination are capable of detoxifying immunogenic gluten peptides in a novel treatment of celiac disease.

5 Clinical Trial Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. 2017

Alshiekh, S / Zhao, L P / Lernmark, Å / Geraghty, D E / Naluai, Å T / Agardh, D. ·Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, Malmö, Sweden. · Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. · Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Waltham. · Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Waltham. · Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. ·HLA · Pubmed #28585303.

ABSTRACT: Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value < .0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P < .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity.

6 Article Directed-Mutagenesis of 2020

Osorio, Claudia E / Wen, Nuan / Mejías, Jaime H / Mitchell, Shannon / von Wettstein, Diter / Rustgi, Sachin. ·Department of Crop and Soil Sciences, Washington State University, Pullman, WA, United States. · Agriaquaculture Nutritional Genomic Center, Temuco, Chile. · Centro Regional de Investigación Carillanca, Instituto de Investigaciones Agropecuarias INIA, Temuco, Chile. · Department of Biological Systems Engineering, Washington State University, Pullman, WA, United States. · Department of Plant and Environmental Sciences, Clemson University Pee Dee Research and Education Center, Florence, SC, United States. ·Front Nutr · Pubmed #32133368.

ABSTRACT: Wheat gluten proteins are the known cause of celiac disease. The repetitive tracts of proline and glutamine residues in these proteins make them exceptionally resilient to digestion in the gastrointestinal tract. These indigested peptides trigger immune reactions in susceptible individuals, which could be either an allergic reaction or celiac disease. Gluten exclusion diet is the only approved remedy for such disorders. Recently, a combination of a glutamine specific endoprotease from barley (EP-B2), and a prolyl endopeptidase from

7 Article Marked coagulopathy without liver disease or anticoagulation therapy. 2019

Jurgensmeier, Kevin / Hixson, Lee J / Pfeiffer, David C. ·WWAMI Medical Education Program, University of Washington School of Medicine and the University of Idaho, 875 Perimeter Drive, Moscow, ID, 83844, USA. Electronic address: kjurgens@uw.edu. · St Joseph Regional Medical Center, 1630 23(rd) Ave. Ste 701, Lewiston, ID, 83501, USA. Electronic address: hixsonvk@gmail.com. · WWAMI Medical Education Program and Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, Moscow, ID, 83844-3051, USA. Electronic address: dpfeiffer@uidaho.edu. ·Clin Res Hepatol Gastroenterol · Pubmed #31884002.

ABSTRACT: Symptomatic coagulopathies in celiac disease (CD) are rare. Here, we report a profound case of coagulopathy in a celiac. A 66-year old female without liver disease or anti-coagulation therapy presented with multiple ecchymoses, guaiac positive melanic stool, and a recent 4.5kg weight loss. Laboratory values included hemoglobin, 3.8g/dL; MCV, 66 fL; serum iron, 17μg/dL; platelet count, 580K/μL; white count, 14.2K/μL, and vitamin D,<5.0ng/mL. Additional values included partial thromboplastin time (PTT), >200s; prothrombin time (PT), >150s; INR, 20.5, putting her at extreme risk of bleeding. Vitamin K deficiency was assumed. The patient was given two units of fresh frozen plasma, packed red cells, and vitamin K intravenously. Endoscopy and biopsies demonstrated duodenal mucosal atrophy with cobblestoning, erosive gastritis, flattened duodenal villi and numerous intraepithelial lymphocytes. Transglutaminase serology demonstrated IgA TTG>100 U/mL (normal<3U/mL), confirming a diagnosis of CD. The patient's coagulopathy resolved within two days following admission. This case underscores the importance of CD testing in all patients with coagulopathies of unknown origin. Although coagulopathy is an uncommon presentation of CD, in extreme cases such as this, it has the potential to be life-threatening.

8 Article Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk. 2019

Andrén Aronsson, Carin / Lee, Hye-Seung / Hård Af Segerstad, Elin M / Uusitalo, Ulla / Yang, Jimin / Koletzko, Sibylle / Liu, Edwin / Kurppa, Kalle / Bingley, Polly J / Toppari, Jorma / Ziegler, Anette G / She, Jin-Xiong / Hagopian, William A / Rewers, Marian / Akolkar, Beena / Krischer, Jeffrey P / Virtanen, Suvi M / Norris, Jill M / Agardh, Daniel / Anonymous2931083. ·Department of Clinical Sciences, Lund University, Malmö, Sweden. · Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa. · Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany. · University of Warmia and Mazuri, Olsztyn, Poland. · Digestive Health Institute, University of Colorado Denver, Children's Hospital Colorado, Denver. · Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland. · 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. · Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes eV, Neuherberg, Germany. · Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia. · Pacific Northwest Diabetes Research Institute, Seattle, Washington. · Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora. · National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. · National Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland. · Faculty of Social Sciences/Health Sciences, University of Tampere, Tampere, Finland. · Research Center for Child Health, Tampere University, University Hospital, Science Center of Pirkanmaa Hospital District, Tampere, Finland. · Colorado School of Public Health, Department of Epidemiology, University of Colorado, Aurora. ·JAMA · Pubmed #31408136.

ABSTRACT: Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

9 Article Early Probiotic Supplementation and the Risk of Celiac Disease in Children at Genetic Risk. 2019

Uusitalo, Ulla / Andren Aronsson, Carin / Liu, Xiang / Kurppa, Kalle / Yang, Jimin / Liu, Edwin / Skidmore, Jennifer / Winkler, Christiane / Rewers, Marian J / Hagopian, William A / She, Jin-Xiong / Toppari, Jorma / Ziegler, Anette-G / Akolkar, Beena / Norris, Jill M / Virtanen, Suvi M / Krischer, Jeffrey P / Agardh, Daniel / Anonymous1141059. ·Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. ulla.uusitalo@epi.usf.edu. · The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 214 28 Malmö, Sweden. · Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. · Tampere Center for Child Health Research, University of Tampere, 33014 Tampere, Finland. · The University Consortium of Seinäjoki, 60320 Seinäjoki, Finland. · Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver, Aurora, CO 80045, USA. · Pacific Northwest Research Institute, Seattle, WA 98122, USA. · Institute of Diabetes Research, Helmholtz Zentrum München, 85764 Munich-Neuherberg, Germany. · Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, 80804 Munich, Germany. · Forschergruppe Diabetes e.V., Helmholtz Zentrum München, 85764 Munich-Neuherberg, Germany. · Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045, USA. · Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. · Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland. · Department of Pediatrics, Turku University Hospital, 20521 Turku, Finland. · NIDDK, National Institute of Health, Bethesda, MD 20892, USA. · Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO 80045, USA. · Unit of Nutrition, National Institute for Health and Welfare, 00271 Helsinki, Finland. · Tampere University Hospital, and the Science Center of Pirkanmaa Hospital District, 33520 Tampere, Finland. ·Nutrients · Pubmed #31382440.

ABSTRACT: Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (

10 Article Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense. 2019

Hung, Shu-Chen / Hou, Tieying / Jiang, Wei / Wang, Nan / Qiao, Shuo-Wang / Chow, I-Ting / Liu, Xiaodan / van der Burg, Sjoerd H / Koelle, David M / Kwok, William W / Sollid, Ludvig M / Mellins, Elizabeth D. ·Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305. · Program in Immunology, Stanford University, Stanford, CA 94305. · Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway. · K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, 0424 Oslo, Norway. · Benaroya Research Institute at Virginia Mason, Seattle, WA 98101. · Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands. · Department of Medicine, University of Washington, Seattle, WA 98195. · Department of Laboratory Medicine, University of Washington, Seattle, WA 98195; and. · Department of Global Health, University of Washington, Seattle, WA 98195. · Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305; mellins@stanford.edu. ·J Immunol · Pubmed #30926644.

ABSTRACT: We have reported that the major histocompatibility molecule HLA-DQ2 (DQA1*05:01/DQB1*02:01) (DQ2) is relatively resistant to HLA-DM (DM), a peptide exchange catalyst for MHC class II. In this study, we analyzed the role of DQ2/DM interaction in the generation of DQ2-restricted gliadin epitopes, relevant to celiac disease, or DQ2-restricted viral epitopes, relevant to host defense. We used paired human APC, differing in DM expression (DM

11 Article Deamidated gliadin peptide in pediatric patients with moderately increased tissue transglutaminase; does it help? 2019

Dickerson, Jane A / Lee, Dale / Pacheco, M Cristina. ·Department of Laboratories, Seattle Children's Hospital, United States; Department of Laboratory Medicine, University of Washington, United States. Electronic address: Jane.dickerson@seattlechildrens.org. · Department of Gastroenterology, Seattle Children's Hospital, United States; Department of Pediatrics, University of Washington, United States. · Department of Laboratories, Seattle Children's Hospital, United States; Department of Anatomic Pathology, University of Washington, United States. ·Clin Chim Acta · Pubmed #30726722.

ABSTRACT: BACKGROUND: Deamidated gliadin peptide (DGP) is a relatively new serologic assay used in diagnosis and monitoring of celiac disease. DGP IgG is recommended by some in pediatric patients <2 y. Use in other pediatric populations is not well established. The utility of the DGP screen (IgG + IgA) in patients with moderate increase of tissue transglutaminase (TTG) IgA has not been studied. METHODS: Cases between January 2015 and October 2017 in which a patient had TTG IgA greater >19 and <100, DGP screen, and biopsy were collected. Indication for biopsy and diabetes diagnosis were recorded. Of 495 patients screened, 31 met criteria. RESULTS: The sensitivity and specificity of DGP screen were calculated, and were 87.4% and 56%, respectively; though lower in patients with diabetes. CONCLUSIONS: The study suggests in patients with moderately increased TTG-IgA, DGP screen lacks specificity and does not provide additional information about whether or not to biopsy.

12 Article Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease. 2019

Osorio, Claudia E / Wen, Nuan / Mejias, Jaime H / Liu, Bao / Reinbothe, Stephen / von Wettstein, Diter / Rustgi, Sachin. ·Department of Crop and Soil Sciences, Washington State University, Pullman, WA, 99164, USA. · Centro de Genómica Nutricional Agro-acuícola, CGNA, Las Heras 350, Temuco, Chile. · Instituto de Investigaciones Agropecuarias (INIA), Centro Regional de Investigación Carillanca, P.O. Box 58-D, Temuco, Chile. · Key Laboratory of Molecular Epigenetics of MOE and Institute of Genetics & Cytology, Northeast Normal University, Changchun, 130024, China. · Laboratoire de Génétique Moléculaire des Plantes et Biologie Environnementale et Systemique (BEeSy), LBFA, Université Grenoble-Alpes, BP53, F-38041, Grenoble cedex 9, France. · Department of Crop and Soil Sciences, Washington State University, Pullman, WA, 99164, USA. srustgi@clemson.edu. · Clemson University Pee Dee Research and Education Center, Florence, SC, 29506, USA. srustgi@clemson.edu. ·Funct Integr Genomics · Pubmed #30159724.

ABSTRACT: Ubiquitous nature of prolamin proteins dubbed gluten from wheat and allied cereals imposes a major challenge in the treatment of celiac disease, an autoimmune disorder with no known treatment other than abstinence diet. Administration of hydrolytic glutenases as food supplement is an alternative to deliver the therapeutic agents directly to the small intestine, where sensitization of immune system and downstream reactions take place. The aim of the present research was to evaluate the capacity of wheat grain to express and store hydrolytic enzymes capable of gluten detoxification. For this purpose, wheat scutellar calli were biolistically transformed to generate plants expressing a combination of glutenase genes for prolamin detoxification. Digestion of prolamins with barley endoprotease B2 (EP-HvB2) combined with Flavobacterium meningosepticum prolyl endopeptidase (PE-FmPep) or Pyrococcus furiosus prolyl endopeptidase (PE-PfuPep) significantly reduced (up to 67%) the amount of the indigestible gluten peptides of all prolamin families tested. Seven of the 168 generated lines showed inheritance of transgene to the T

13 Article A woman with a 10 year history of abdominal pain. 2018

Richelieu, Jessica / Morse, John Wi / Pfeiffer, David C. ·University of Washington School of Medicine, Seattle, Washington, USA. · Kings Lane Medical Clinic, Salt Spring Island, British Columbia, Canada. · Department of Biological Sciences and WWAMI Medical Education Program, University of Idaho, Moscow, Idaho, USA dpfeiffer@uidaho.edu. ·BMJ · Pubmed #29599283.

ABSTRACT: -- No abstract --

14 Article Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study. 2018

Koletzko, Sibylle / Lee, Hye-Seung / Beyerlein, Andreas / Aronsson, Carin A / Hummel, Michael / Liu, Edwin / Simell, Ville / Kurppa, Kalle / Lernmark, Åke / Hagopian, William / Rewers, Marian / She, Jin-Xiong / Simell, Olli / Toppari, Jorma / Ziegler, Anette-G / Krischer, Jeffrey / Agardh, Daniel / Anonymous8211111. ·*Dr. v. Hauner Children's Hospital, University Munich Medical Center, Munich, Germany †Health Informatics Institute, Department of Paediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA ‡Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany §Department of Clinical Sciences, Lund University, Skane University Hosptial, Malmo, Sweden ||Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Aurora, CO, USA ¶Medicity Laboratory, University of Turku, Turku, Finland #Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland **Pacific Northwest Diabetes Research Institute, Seattle WA, USA ††Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora CO, USA ‡‡Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta GA, USA §§Department of Paediatrics, Turku University Hospital, Turku, Finland ||||Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland ¶¶Departments of Physiology, University of Turku, Turku, Finland. ·J Pediatr Gastroenterol Nutr · Pubmed #28753178.

ABSTRACT: OBJECTIVE: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. METHODS: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. CONCLUSION: C-section is not associated with increased risk for CDA or CD in the offspring.

15 Article Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. 2017

Kemppainen, Kaisa M / Vehik, Kendra / Lynch, Kristian F / Larsson, Helena Elding / Canepa, Ronald J / Simell, Ville / Koletzko, Sibylle / Liu, Edwin / Simell, Olli G / Toppari, Jorma / Ziegler, Anette G / Rewers, Marian J / Lernmark, Åke / Hagopian, William A / She, Jin-Xiong / Akolkar, Beena / Schatz, Desmond A / Atkinson, Mark A / Blaser, Martin J / Krischer, Jeffrey P / Hyöty, Heikki / Agardh, Daniel / Triplett, Eric W / Anonymous1080924. ·Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville. · Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa. · Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden. · MediCity Laboratory, University of Turku, Turku, Finland. · Division of Paediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Ludwig Maximilian University, München, Germany. · Digestive Health Institute, Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado Denver, Aurora. · Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. · Department of Pediatrics, University of Turku, Turku University Hospital, Turku, Finland. · Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland. · Institute of Diabetes Research, Helmholtz Zentrum München, München, Germany. · Klinikum Rechts der Isar, Technische Universität München, München, Germany. · Forschergruppe Diabetes e.V., Neuherberg, Germany. · Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora. · Pacific Northwest Diabetes Research Institute, Seattle, Washington. · Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta. · National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. · Department of Pediatrics, College of Medicine, University of Florida, Gainesville. · Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville. · Department of Medicine and Microbiology, New York School of Medicine, New York. · Department of Virology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. · Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland. ·JAMA Pediatr · Pubmed #29052687.

ABSTRACT: Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases. Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD. Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D. Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively. Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity. Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 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). Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.

16 Article Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity. 2017

Hagopian, William / Lee, Hye-Seung / Liu, Edwin / Rewers, Marian / She, Jin-Xiong / Ziegler, Anette-G / Lernmark, Åke / Toppari, Jorma / Rich, Stephen S / Krischer, Jeffrey P / Erlich, Henry / Akolkar, Beena / Agardh, Daniel / Anonymous10101111. ·Diabetes Programs Division, Pacific Northwest Research Institute, Seattle, Washington; wah@uw.edu. · Department of Pediatrics, Health Informatics Institute, University of South Florida, Tampa, Florida. · Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, Colorado. · Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia. · Institute of Diabetes Research, Helmholtz Zentrum München, Oberschleißheim, Germany. · Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. · Department of Pediatrics, Turku University Central Hospital, Turku, Finland. · Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia. · Children's Hospital of Oakland Research Institute, Oakland, California; and. · Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. ·Pediatrics · Pubmed #29018046.

ABSTRACT: BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors. METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed. RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors. CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.

17 Article Maternal use of dietary supplements during pregnancy is not associated with coeliac disease in the offspring: The Environmental Determinants of Diabetes in the Young (TEDDY) study. 2017

Yang, Jimin / Tamura, Roy N / Aronsson, Carin A / Uusitalo, Ulla M / Lernmark, Åke / Rewers, Marian / Hagopian, William A / She, Jin-Xiong / Toppari, Jorma / Ziegler, Anette G / Akolkar, Beena / Krischer, Jeffrey P / Norris, Jill M / Virtanen, Suvi M / Agardh, Daniel / Anonymous4221111. ·1Health Informatics Institute,Morsani College of Medicine,University of South Florida,Tampa,FL 33612,USA. · 2The Diabetes and Celiac Disease Unit,Department of Clinical Sciences,Lund University,20502 Malmö,Sweden. · 3Barbara Davis Center for Childhood Diabetes,University of Colorado School of Medicine,Aurora,CO 80045,USA. · 4Pacific Northwest Diabetes Research Institute,Seattle,WA 98122,USA. · 5Center for Biotechnology and Genomic Medicine,Augusta University,Augusta,GA 30912,USA. · 6Department of Physiology,Institute of Biomedicine,University of Turku,20014 Turku,Finland. · 8Institute of Diabetes Research,Helmholtz Zentrum München and Klinikum rechts der Isar,Technische Universität München, and Forschergruppe Diabetes e.V.,80804 Neuherberg,Germany. · 9National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MA 20892,USA. · 10Department of Epidemiology,Colorado School of Public Health,University of Colorado Anschutz Medical Campus,Aurora,CO 80045,USA. · 11Unit of Nutrition,National Institute for Health and Welfare,00300 Helsinki,Finland. ·Br J Nutr · Pubmed #28249640.

ABSTRACT: Perinatal exposure to nutrients and dietary components may affect the risk for coeliac disease (CD). We investigated the association between maternal use of vitamin D, n-3 fatty acids (FA) and Fe supplements during pregnancy and risk for CD autoimmunity (CDA) and CD in the offspring. Children at increased genetic risk were prospectively followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. CDA was defined as having persistently positive tissue transglutaminase autoantibodies (tTGA). Diagnosis of CD was either biopsy-confirmed or considered likely if having persistently elevated levels of tTGA>100 AU. Of 6627 enrolled children, 1136 developed CDA at a median 3·1 years of age (range 0·9-10) and 409 developed CD at a median 3·9 years of age (range 1·2-11). Use of supplements containing vitamin D, n-3 FA and Fe was recalled by 66, 17 and 94 % of mothers, respectively, at 3-4 months postpartum. The mean cumulative intake over the entire pregnancy was 2014 μg vitamin D (sd 2045 μg), 111 g n-3 FA (sd 303 g) and 8806 mg Fe (sd 7017 mg). After adjusting for country, child's human leucocyte antigen genotype, sex, family history of CD, any breast-feeding duration and household crowding, Cox's proportional hazard ratios did not suggest a statistically significant association between the intake of vitamin D, n-3 FA or Fe, and risk for CDA or CD. Dietary supplementation during pregnancy may help boost nutrient intake, but it is not likely to modify the risk for the disease in the offspring.

18 Article The Celiac Patient Antibody Response to Conventional and Gluten-Removed Beer. 2017

Allred, Laura K / Lesko, Katherine / McKiernan, Diane / Kupper, Cynthia / Guandalini, Stefano. ·Gluten Intolerance Group of North America, Auburn, WA. · The University of Chicago, Biological Sciences Division, Chicago, IL. · The University of Chicago Celiac Disease Center, Chicago, IL. · University of Chicago, Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Chicago, IL. ·J AOAC Int · Pubmed #28118560.

ABSTRACT: Enzymatic digestion, or hydrolysis, has been proposed for treating gluten-containing foods and beverages to make them safe for persons with celiac disease (CD). There are no validated testing methods that allow the quantitation of all the hydrolyzed or fermented gluten peptides in foods and beverages that might be harmful to CD patients, making it difficult to assess the safety of hydrolyzed products. This study examines an ELISA-based method to determine whether serum antibody binding of residual peptides in a fermented barley-based product is greater among active-CD patients than a normal control group, using commercial beers as a test case. Sera from 31 active-CD patients and 29 nonceliac control subjects were used to assess the binding of proteins from barley, rice, traditional beer, gluten-free beer, and enzymatically treated (gluten-removed) traditional beer. In the ELISA, none of the subjects' sera bound to proteins in the gluten-free beer. Eleven active-CD patient serum samples demonstrated immunoglobulin A (IgA) or immunoglobulin G (IgG) binding to a barley extract, compared to only one nonceliac control subject. Of the seven active-CD patients who had an IgA binding response to barley, four also responded to traditional beer, and two of these responded to the gluten-removed beer. None of the nonceliac control subjects' sera bound to all three beer samples. Binding of protein fragments in hydrolyzed or fermented foods and beverages by serum from active-CD patients, but not nonceliac control subjects, may indicate the presence of residual peptides that are celiac-specific.

19 Article Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life. 2017

Kemppainen, Kaisa M / Lynch, Kristian F / Liu, Edwin / Lönnrot, Maria / Simell, Ville / Briese, Thomas / Koletzko, Sibylle / Hagopian, William / Rewers, Marian / She, Jin-Xiong / Simell, Olli / Toppari, Jorma / Ziegler, Anette-G / Akolkar, Beena / Krischer, Jeffrey P / Lernmark, Åke / Hyöty, Heikki / Triplett, Eric W / Agardh, Daniel / Anonymous2050887. ·Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida. · Health Informatics Institute, University of South Florida, Tampa, Florida. · Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Denver; Barbara Davis Center, University of Colorado Denver, Aurora, Colorado. · Department of Virology, School of Medicine, University of Tampere, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland. · MediCity Laboratory, University of Turku, Turku, Finland. · Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. · Dr von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany. · Pacific Northwest Diabetes Research Institute, Seattle, Washington. · Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. · Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. · Department of Pediatrics, University of Turku, Turku, Finland; Departments of Physiology and Pediatrics, University of Turku, Turku, Finland. · Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum Rechts der Isar, Technische Universität München, Forschergruppe Diabetes eV, Neuherberg, Germany. · National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. · Department of Clinical Sciences, Lund University, Malmo, Sweden. · Department of Virology, School of Medicine, University of Tampere, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland. · Department of Clinical Sciences, Lund University, Malmo, Sweden. Electronic address: daniel.agardh@med.lu.se. ·Clin Gastroenterol Hepatol · Pubmed #27840181.

ABSTRACT: BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of gluten immunogenicity in patients with celiac disease. We studied temporal associations between infections and the development of celiac disease autoimmunity, and examined effects of HLA alleles, rotavirus vaccination status, and infant feeding. METHODS: We monitored 6327 children in the United States and Europe carrying HLA risk genotypes for celiac disease from 1 to 4 years of age for presence of tissue transglutaminase autoantibodies (the definition of celiac disease autoimmunity), until March 31, 2015. Parental reports of gastrointestinal and respiratory infections were collected every third month from birth. We analyzed time-varying relationships among reported infections, rotavirus vaccination status, time to first introduction of gluten, breastfeeding, and risk of celiac disease autoimmunity using proportional hazard models. RESULTS: We identified 13,881 gastrointestinal infectious episodes (GIE) and 79,816 respiratory infectious episodes. During the follow-up period, 732 of 6327 (11.6%) children developed celiac disease autoimmunity. A GIE increased the risk of celiac disease autoimmunity within the following 3 months by 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.11-1.59). This risk increased 2-fold among children born in winter and introduced to gluten before age 6 months (HR, 2.08; 95% CI, 1.46-2.98), and increased 10-fold among children without HLA-DQ2 alleles and breastfed for fewer than 4 months (HR, 9.76; 95% CI, 3.87-24.8). Risk of celiac disease autoimmunity was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR, 0.57; 95% CI, 0.36-0.88). CONCLUSIONS: Gastrointestinal infections increase the risk of celiac disease autoimmunity in children with genetic susceptibility to this autoimmune disorder. The risk is modified by HLA genotype, infant gluten consumption, breastfeeding, and rotavirus vaccination, indicating complex interactions among infections, genetic factors, and diet in the etiology of celiac disease in early childhood.

20 Article Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease. 2016

Mohan, Mahesh / Chow, Cheryl-Emiliane T / Ryan, Caitlin N / Chan, Luisa S / Dufour, Jason / Aye, Pyone P / Blanchard, James / Moehs, Charles P / Sestak, Karol. ·Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA. mmohan@tulane.edu. · Second Genome Inc., San Francisco, CA 94080, USA. cheryl@secondgenome.com. · Second Genome Inc., San Francisco, CA 94080, USA. caitlin@secondgenome.com. · Second Genome Inc., San Francisco, CA 94080, USA. luisa@secondgenome.com. · Division of Veterinary Resources, Tulane National Primate Research Center, Covington, LA 70433, USA. jdufour@tulane.edu. · Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA. paye@tulane.edu. · Division of Veterinary Resources, Tulane National Primate Research Center, Covington, LA 70433, USA. paye@tulane.edu. · Division of Veterinary Resources, Tulane National Primate Research Center, Covington, LA 70433, USA. jblanch1@tulane.edu. · Arcadia Biosciences Inc., Seattle, WA 98119, USA. max.moehs@arcadiabio.com. · Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA. ksestak@tulane.edu. · PreCliniTria LLC, Mandeville, LA 70471, USA. ksestak@tulane.edu. ·Nutrients · Pubmed #27801835.

ABSTRACT: The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (

21 Article Supplementation of Reduced Gluten Barley Diet with Oral Prolyl Endopeptidase Effectively Abrogates Enteropathy-Associated Changes in Gluten-Sensitive Macaques. 2016

Sestak, Karol / Thwin, Hazel / Dufour, Jason / Liu, David X / Alvarez, Xavier / Laine, David / Clarke, Adam / Doyle, Anthony / Aye, Pyone P / Blanchard, James / Moehs, Charles P. ·Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA. ksestak@tulane.edu. · PreCliniTria, LLC., Mandeville, LA 70471, USA. ksestak@tulane.edu. · Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA. hthwin@tulane.edu. · Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA 70433, USA. jdufour@tulane.edu. · Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA. dliu1@tulane.edu. · Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA. Xavier@tulane.edu. · TEVA Biologics, Discovery & Development, Sydney, Macquarie Park 2113, NSW, Australia. David.Laine@tevapharm.com. · TEVA Biologics, Discovery & Development, Sydney, Macquarie Park 2113, NSW, Australia. Adam.Clarke@tevapharm.com. · TEVA Biologics, Discovery & Development, Sydney, Macquarie Park 2113, NSW, Australia. Anthony.Doyle@tevapharm.com. · Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA 70433, USA. paye@tulane.edu. · Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA. paye@tulane.edu. · Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA 70433, USA. jblanch1@tulane.edu. · Arcadia Biosciences Inc., Seattle, WA 98119, USA. max.moehs@arcadiabio.com. ·Nutrients · Pubmed #27367722.

ABSTRACT: Celiac disease (CD) is an autoimmune disorder that affects approximately three million people in the United States. Furthermore, non-celiac gluten sensitivity (NCGS) affects an estimated additional 6% of the population, e.g., 20 million in the U.S. The only effective treatment of CD and NCGS requires complete removal of gluten sources from the diet. While required adherence to a gluten-free diet (GFD) is extremely difficult to accomplish, efforts to develop additional supportive treatments are needed. To facilitate these efforts, we developed a gluten-sensitive (GS) rhesus macaque model to study the effects of novel therapies. Recently reported results from phase one of this project suggest that partial improvement-but not remission-of gluten-induced disease can be accomplished by 100-fold reduction of dietary gluten, i.e., 200 ppm-by replacement of conventional dietary sources of gluten with a mutant, reduced gluten (RG) barley (lys3a)-derived source. The main focus of this (phase two) study was to determine if the inflammatory effects of the residual gluten in lys3a mutant barley grain could be further reduced by oral supplementation with a prolylendopeptidase (PE). Results reveal that PE supplementation of RG barley diet induces more complete immunological, histopathological and clinical remission than RG barley diet alone. The combined effects of RG barley diet and PE supplementation resulted in a further decrease of inflammatory mediators IFN-γ and TNF secretion by peripheral lymphocytes, as well as decreased plasma anti-gliadin and anti-intestinal tissue transglutaminase (TG2) antibodies, diminished active caspase production in small intestinal mucosa, and eliminated clinical diarrhea-all comparable with a gluten-free diet induced remission. In summary, the beneficial results of a combined RG barley and PE administration in GS macaques may warrant the investigation of similar synergistic approaches.

22 Article Novel Monoclonal Antibody-Based Immunodiagnostic Assay for Rapid Detection of Deamidated Gluten Residues. 2016

Masiri, Jongkit / Benoit, Lora / Katepalli, Madhu / Meshgi, Mahzad / Cox, David / Nadala, Cesar / Sung, Shao-Lei / Samadpour, Mansour. ·Molecular Epidemiology, Inc. (MEI) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States. · IEH Laboratories and Consulting Group, Inc. (IEH) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States. · Pi Bioscientific, Inc. (Pi Bio) , 8315 Lake City Way N.E., Seattle, Washington 98115, United States. ·J Agric Food Chem · Pubmed #27087556.

ABSTRACT: Gluten derived from wheat and related Triticeae can induce gluten sensitivity as well as celiac disease. Consequently, gluten content in foods labeled "gluten-free" is regulated. Determination of potential contamination in such foods is achieved using immunoassays based on monoclonal antibodies (mAbs) that recognize specific epitopes present in gluten. However, food-processing measures can affect epitope recognition. In particular, preparation of wheat protein isolate through deamidation of glutamine residues significantly limits the ability of commercial gluten testing kits in their ability to recognize gluten. Adding to this concern, evidence suggests that deamidated gluten imparts more pathogenic potential in celiac disease than native gluten. To address the heightened need for antibody-based tools that can recognize deamidated gluten, we have generated a novel mAb, 2B9, and subsequently developed it as a rapid lateral flow immunoassay. Herein, we report the ability of the 2B9-based lateral flow device (LFD) to detect gluten from wheat, barley, and rye and deamidated gluten down to 2 ppm in food as well as its performance in food testing.

23 Article Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort. 2016

Sharma, Ashok / Liu, Xiang / Hadley, David / Hagopian, William / Liu, Edwin / Chen, Wei-Min / Onengut-Gumuscu, Suna / Simell, Ville / Rewers, Marian / Ziegler, Anette-G / Lernmark, Åke / Simell, Olli / Toppari, Jorma / Krischer, Jeffrey P / Akolkar, Beena / Rich, Stephen S / Agardh, Daniel / She, Jin-Xiong / Anonymous5430862. ·Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA, United States of America. · Pediatric Epidemiology Center, Department of Pediatrics, University of South Florida, Tampa, FL, United States of America. · Division of Population Health Sciences and Education, St George's University of London, London, United Kingdom. · Pacific Northwest Diabetes Research Institute, Seattle, WA, United States of America. · Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver, Aurora, CO, United States of America. · Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America. · Department of Pediatrics, University of Turku, Turku, Finland. · Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, United States of America. · Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Munich-Neuherberg, Germany. · Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden. · National Institutes of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD, United States of America. · Diabetes and Celiac Disease Unit, Lund University, Malmo, Sweden. ·PLoS One · Pubmed #27015091.

ABSTRACT: OBJECTIVES: There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study. METHODS: A total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses. RESULTS: We found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10-4>P>5.8x10-6). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10-4). A SNP near PKIA (rs117128341, P = 6.5x10-8, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10-7, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10-6, HR = 0.76 and LPP, P = 2.8x10-5, HR = .80) and 6 SNPs in 5 regions not previously associated with celiac disease (P<10-4); non-HLA genes are therefore involved in development of tTGA. CONCLUSIONS: In conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.

24 Article Obesity and Cardiovascular Risk in Adults With Celiac Disease. 2016

Stein, Adam C / Liao, Chuanhong / Paski, Shirley / Polonsky, Tamar / Semrad, Carol E / Kupfer, Sonia S. ·*University of Chicago Celiac Disease Center †Department of Health Studies, University of Chicago §Section of Cardiology, University of Chicago, Chicago, IL ‡Department of Medicine, University of Washington, Seattle, WA. ·J Clin Gastroenterol · Pubmed #26444646.

ABSTRACT: BACKGROUND: Patients with celiac disease (CD) may be at an increased risk of cardiovascular disease (CVD), yet CVD risk factors are not well defined in CD. The validated Framingham Heart Study 10-year general CVD risk score (FRS) that incorporates traditional CVD risk factors including body mass index (BMI) has not been previously studied in CD patients. AIMS: To compare BMI and FRS in CD patients with population-based controls. METHODS: Biopsy-proven CD patients were ascertained retrospectively and data on BMI, systolic blood pressure, hypertension, smoking status, and diabetes were obtained at initial and follow-up visits. FRS was calculated and compared with 4 matched general population non-CD controls from the 2009 to 2010 National Health and Nutrition Examination Survey (NHANES). RESULTS: Of 258 total CD patients, 38.3% were overweight or obese compared with 69.8% of controls (P<0.001). In total, 174 CD patients met the inclusion criteria for FRS calculation. Of these, the median FRS was lower in CD patients compared with controls (3.9 vs. 4.2; P=0.011). In CD patients, tobacco use was significantly lower (P<0.001), whereas systolic blood pressure was significantly higher (P<0.01) than controls. CONCLUSIONS: Global CVD risk is lower among patients with CD compared with population controls. Lower BMI and tobacco use among CD patients could account for this difference. These results suggest that factors other than those measured by FRS could contribute to the increased risk of CVD in CD observed in some studies.

25 Article HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study. 2015

Hadley, David / Hagopian, William / Liu, Edwin / She, Jin-Xiong / Simell, Olli / Akolkar, Beena / Ziegler, Anette-G / Rewers, Marian / Krischer, Jeffrey P / Chen, Wei-Min / Onengut-Gumuscu, Suna / Bugawan, Teodorica L / Rich, Stephen S / Erlich, Henry / Agardh, Daniel / Anonymous381111. ·1] Division of Population Health Sciences and Education, St. George's, University of London, London, UK [2] TransMed Systems, Pleasanton, California, USA. · Pacific Northwest Diabetes Research Institute, Seattle, Washington, USA. · 1] Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA [2] Barbara Davis Center, University of Colorado Denver, Aurora, Colorado, USA. · Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, Georgia, USA. · Department of Pediatrics, University of Turku, Turku, Finland. · DDEMD, NIDDK, Bethesda, Maryland, USA. · 1] Institute of Diabetes Research, Helmholtz Zentrum Mìnchen, Oberschleissheim, Germany [2] Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany [3] Forschergruppe Diabetes e.V., Neuherberg, Germany. · Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA. · Pediatric Epidemiology Center, University of South Florida, Tampa, Florida, USA. · Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA. · Department of Human Genetics, Roche Molecular Systems, Alameda, California, USA. · Children's Hospital of Oakland Research Institute, Oakland, California, USA. · 1] Pediatric Epidemiology Center, University of South Florida, Tampa, Florida, USA [2] Department of Clinical Sciences, Lund University, Malmo, Sweden. ·Am J Gastroenterol · Pubmed #26010309.

ABSTRACT: OBJECTIVES: Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. RESULTS: After adjustment for DR3-DQ2 and restriction to allele frequency (AF) ≥5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). CONCLUSIONS: HLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.

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