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Celiac Disease: HELP
Articles from Miscellaneous cities in California
Based on 14 articles published since 2010
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These are the 14 published articles about Celiac Disease that originated from Miscellaneous cities in California during 2010-2020.
 
+ Citations + Abstracts
1 Guideline Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico. 2018

Remes-Troche, J M / Uscanga-Domínguez, L F / Aceves-Tavares, R G / Calderón de la Barca, A M / Carmona-Sánchez, R I / Cerda-Contreras, E / Coss-Adame, E / Icaza-Chávez, M E / Lopéz-Colombo, A / Milke-García, M P / Morales-Arámbula, M / Peláez-Luna, M / Ramos Martínez, P / Sánchez-Sosa, S / Treviño-Mejía, M C / Vázquez-Frías, R / Worona-Dibner, L B / Zamora-Nava, L E / Rubio-Tapia, A. ·Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, México. Electronic address: jose.remes.troche@gmail.com. · Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México. · Servicio de Gastroenterología, Hospital General del Estado Dr. Ernesto Ramos, Bours, Hermosillo, Sonora, México. · Centro de Investigación en Alimentación y Desarrollo, A.C, Hermosillo, Sonora, México. · Unidad de Medicina Ambulatoria Christus Muguerza, , San Luis Potosí, México. · ITESM. Medicina Interna y Gastroenterología Fundación Clínica Médica Sur, Ciudad de México, México. · Departamento de Gastroenterología y Laboratorio de Motilidad Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Ciudad de México, México. · Hospital Star Médica de Mérida, Gastroenterología de la UNIMAYAB, , Mérida, Yucatán, México. · Dirección de Educación e Investigación en Salud, UMAE Hospital de Especialidades del Centro Médico Nacional Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México. · Dirección de Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Ciudad de México, México. · Servicio de Gastroenterología y Endoscopía Gastrointestinal, Hospital Country 2000, Guadalajara, Jalisco, México. · Centro de Patología Especializada, San Luis Potosí, México. · Jefe de Patología, Hospital Ángeles de Puebla, Universidad de Las Américas Puebla (UDLAP), Puebla, México. · Universidad Iberoamericana, Universidad Xochicalco, Tijuana, Baja California, México. · Departamento de Gastroenterología y Nutrición, Hospital Infantil de México Federico Gómez, Ciudad de México, México. · Departamento de Endoscopia Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México. · División de Gastroenterología y Hepatología, Mayo Clinic, Rochester, Minnesota, Estados Unidos de América. ·Rev Gastroenterol Mex · Pubmed #30197183.

ABSTRACT: Celiac disease, celiac sprue, or gluten-sensitive enteropathy, is a generalized autoimmune disease characterized by chronic inflammation and atrophy of the small bowel mucosa. It is caused by dietary exposure to gluten and affects genetically predisposed individuals. In Mexico, at least 800,000 are estimated to possibly have the disease, prompting the Asociación Mexicana de Gastroenterología to summon a multidisciplinary group of experts to develop the "Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico" and establish recommendations for the medical community, its patients, and the general population. The participating medical professionals were divided into three working groups and were given the selected bibliographic material by the coordinators (ART, LUD, JMRT), who proposed the statements that were discussed and voted upon in three sessions: two voting rounds were carried out electronically and one at a face-to-face meeting. Thirty-nine statements were accepted, and once approved, were developed and revised by the coordinators, and their final version was approved by all the participants. It was emphasized in the document that epidemiology and risk factors associated with celiac disease (first-degree relatives, autoimmune diseases, high-risk populations) in Mexico are similar to those described in other parts of the world. Standards for diagnosing the disease and its appropriate treatment in the Mexican patient were established. The guidelines also highlighted the fact that a strict gluten-free diet is essential only in persons with confirmed celiac disease, and that the role of gluten is still a subject of debate in relation to nonceliac, gluten-sensitive patients.

2 Clinical Trial No Difference Between Latiglutenase and Placebo in Reducing Villous Atrophy or Improving Symptoms in Patients With Symptomatic Celiac Disease. 2017

Murray, Joseph A / Kelly, Ciarán P / Green, Peter H R / Marcantonio, Annette / Wu, Tsung-Teh / Mäki, Markku / Adelman, Daniel C / Anonymous6950887. ·Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: murray.joseph@mayo.edu. · Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Columbia University College of Physicians and Surgeons, New York, New York. · Alvine Pharmaceuticals, San Carlos, California. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. · School of Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland. ·Gastroenterology · Pubmed #27864127.

ABSTRACT: BACKGROUND & AIMS: Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Nondietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsy specimens from patients with celiac disease. METHODS: We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atrophy (villous height:crypt depth ratio of ≤2.0) were assigned randomly to groups given placebo or 100, 300, 450, 600, or 900 mg latiglutenase daily for 12 or 24 weeks. Subjects completed the Celiac Disease Symptom Diary each day for 28 days and underwent an upper gastrointestinal endoscopy with duodenal biopsy of the distal duodenum at baseline and at weeks 12 and 24. The primary end point was a change in the villous height:crypt depth ratio. Secondary end points included numbers of intraepithelial lymphocytes, serology test results (for levels of antibodies against tissue transglutaminase-2 and deamidated gliadin peptide), symptom frequencies, and safety. RESULTS: In a modified intent-to-treat population, there were no differences between latiglutenase and placebo groups in change from baseline in villous height:crypt depth ratio, numbers of intraepithelial lymphocytes, or serologic markers of celiac disease. All groups had significant improvements in histologic and symptom scores. CONCLUSIONS: In a phase 2 study of patients with symptomatic celiac disease and histologic evidence of significant duodenal mucosal injury, latiglutenase did not improve histologic and symptom scores when compared with placebo. There were no significant differences in change from baseline between groups. ClinicalTrials.gov no: NCT01917630.

3 Clinical Trial Safety, tolerability, and activity of ALV003: results from two phase 1 single, escalating-dose clinical trials. 2012

Siegel, Matthew / Garber, Mitchell E / Spencer, Andrew G / Botwick, Wendy / Kumar, Pawan / Williams, Robert N / Kozuka, Kenji / Shreeniwas, Revati / Pratha, Vijaya / Adelman, Daniel C. ·Alvine Pharmaceuticals, 75 Shoreway Road, Suite B, San Carlos, CA 94070, USA. msiegel@alvinepharma.com ·Dig Dis Sci · Pubmed #21948339.

ABSTRACT: BACKGROUND: Celiac disease is the most common hereditary autoimmune disease in humans. The only treatment option for non-refractory celiac disease patients is adherence to a strict life-long gluten-free diet, which often fails to normalize small bowel histology. ALV003 is a mixture of two proteases that degrades gluten and is in clinical development as an oral therapy for patients with celiac disease. AIMS: The safety, tolerability, and activity of ALV003 were assessed in two phase 1 clinical trials. METHODS: In study 1 (N = 28) the study drug was administered in the fasted state; in study 2 (N = 53) the study drug was administered together with a gluten-containing meal. Both studies were single-dose, single-blind, placebo-controlled, cross-over trials. ALV003 was dosed at escalating dose levels by cohort (100, 300, 900, and 1,800 mg) and gastric samples were aspirated using a nasogastric tube. Adverse events, serum drug levels, and anti-drug antibody titers were measured. Gastric samples were assessed for ALV003 enzymatic activity over time (gastric pharmacokinetics) and gluten degradation (gastric pharmacodynamics). RESULTS: All doses were well tolerated, and no serious adverse events or allergic reactions were observed. Gastric aspirates collected 30 min following a meal showed that 100 and 300 mg ALV003 degraded 75 ± 10% (N = 8) and 88 ± 5% (N = 8), respectively, of one gram of wheat bread gluten. CONCLUSIONS: ALV003 is an orally active protease that appears to be stable in the fed stomach and degrades dietary gluten in this compartment. Single doses of oral ALV003 were not associated with serious adverse reactions.

4 Article Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders. 2019

Yang, Yuanyuan / Deshpande, Payal / Krishna, Karthik / Ranganathan, Vinodh / Jayaraman, Vasanth / Wang, Tianhao / Bei, Kang / Rajasekaran, John J / Krishnamurthy, Hari. ·Vibrant America LLC., San Carlos, CA, USA. · Vibrant Sciences, LLC., San Carlos, CA, USA. ·Dis Markers · Pubmed #30755781.

ABSTRACT: Background and Aims: Rheumatoid arthritis (RA) and celiac disease (CD) are members of the autoimmune disease family while they have been shown to share multiple aspects in epidemiology and clinical manifestations. The aim of this study was to assess the presence of wheat protein antibodies in RA seropositive subjects and the presence of RA diagnostic markers in subjects with seropositive wheat-related disorders including CD. Methods: Serum samples were collected from 844 subjects with joint pain and/or gastrointestinal symptoms and tested by a CD panel (anti-tTG and anti-DGP), a Wheat Zoomer (WZ) antibody panel (IgG/IgA to 14 wheat proteins), and a RA panel (anti-CCP and anti-RF). Retrospective analysis was completed using de-identified clinical data and test results. Results: The prevalence of RA markers was first investigated in CD- or WZ-positive subjects and negative controls. 49 subjects were seropositive in the CD panel with 10 (20%) RA positivity. 605 subjects were seropositive in the WZ panel with 106 (18%) RA positivity. 222 subjects were seronegative in either panels with 12 (6%) RA positivity. Next, the frequency of the CD markers and the clinically relevant wheat protein antibodies were investigated in the RA-positive subjects and negative controls. 128 subjects in this cohort were seropositive in the RA panel with 10 (8%) CD positivity and 106 (83%) WZ positivity, compared to 716 RA seronegative controls with 39 (5%) CD positivity and 499 (70%) WZ positivity. Conclusions: Our data presents an apparent trend of overlapped serological antibody biomarker positivity in RA and wheat-related disorders.

5 Article Synthetic Neoepitopes of the Transglutaminase-Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease. 2019

Choung, Rok Seon / Khaleghi Rostamkolaei, Shahryar / Ju, Josephine M / Marietta, Eric V / Van Dyke, Carol T / Rajasekaran, J J / Jayaraman, Vasanth / Wang, Tianhao / Bei, Kang / Rajasekaran, Karenah E / Krishna, Karthik / Krishnamurthy, Hari Krishnan / Murray, Joseph A. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. · Vibrant Sciences LLC, San Carlos, California. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: murray.joseph@mayo.edu. ·Gastroenterology · Pubmed #30342033.

ABSTRACT: BACKGROUND & AIMS: Celiac disease (CeD) has characteristics of an autoimmune disease, such as increased antibody levels to tissue transglutaminase (tTG). However, assays to measure these biomarkers in blood samples do not identify patients with sufficient accuracy for diagnosis or monitoring of CeD. We aimed to discover biomarkers of CeD derived from neoepitopes of deamidated gliadin peptides (DGP) and tTG fragments and to determine if immune reactivity against these epitopes can identify patients with CeD with mucosal healing. METHODS: We analyzed serum samples from 90 patients with biopsy-proven CeD and 79 healthy individuals (controls) for immune reactivity against the tTG-DGP complex (discovery cohort). A fluorescent peptide microarray platform was used to estimate the antibody-binding intensity of each synthesized tTG-DGP epitope. We validated our findings in 82 patients with newly diagnosed CeD and 217 controls. We tested the ability of our peptide panel to identify patients with mucosal healing (based on the histologic analysis) using serum samples from patients with treated and healed CeD (n = 85), patients with treated but unhealed CeD (n = 81; villous atrophy despite a adhering a gluten-free diet), patients with untreated CeD (n = 82) and disease controls (n = 27), villous atrophy without CeD), and healthy controls (n = 217). Data were analyzed using principal component analysis followed by machine learning and support vector machine modeling. RESULTS: We identified 172 immunogenic epitopes of the tTG-DGP complex. We found significantly increased immune reactivity against these epitopes vs controls. In the both cohort, the set of neoepitopes derived from the tTG-DGP complex identified patients with CeD with 99% sensitivity and 100% specificity. Serum samples from patients with untreated CeD had the greatest mean antibody-binding intensity against the tTG-DGP complex (32.5 ± 16.4). The average antibody-binding intensity was significantly higher in serum from patients with treated but unhealed CeD mucosa (15.1 ± 7.5) than in patients with treated and healed CeD mucosa (5.5 ± 3.4) (P < .001). The assay identified patients with mucosa healing status with 84% sensitivity and 95% specificity. CONCLUSIONS: We identified immunogenic epitopes of the tTG-DGP complex, and found that an assay to measure the immune response to epitopes accurately identified patients with CeD, as well as patients with mucosal healing. This biomarker assay might be used in detection and monitoring of patients with CeD.

6 Article Numbers and Features of Patients With a Diagnosis of Celiac Disease Without Duodenal Biopsy, Based on a National Survey. 2019

Joelson, Andrew M / Geller, Marilyn G / Zylberberg, Haley M / Green, Peter H R / Lebwohl, Benjamin. ·Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York. · Celiac Disease Foundation, Woodland Hills, California. · Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York; Deartment of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, New York. Electronic address: BL114@columbia.edu. ·Clin Gastroenterol Hepatol · Pubmed #30213582.

ABSTRACT: BACKGROUND & AIMS: According to guidelines, individuals with symptoms of celiac disease should undergo duodenal biopsy analysis to establish a diagnosis, but little is known about physician adherence to these guidelines. We used a patient-powered research network (PPRN) to compare demographics, diagnoses, symptoms, and treatment between groups of patients with celiac disease diagnosed by biopsy analysis and patients with a diagnosis based on results of serology tests. METHODS: We analyzed data from iCureCeliac-a voluntary, PPRN hosted and distributed by the Celiac Disease Foundation, from January 30, 2016, through August 25, 2016. We compared data from adults with a diagnosis of celiac disease (mean age, 43.4 years; 85.6% female) based on biopsy analysis (n = 780) vs patients with a diagnosis based on only serologic analysis (n = 202) using univariate and multivariable analyses. We collected demographic information, as well as data on type of health care practitioner, where patients obtain their primary information about celiac disease, and the Celiac Disease Quality of Life score, nutritionist referral rates, adherence to the gluten-free diet, ongoing symptoms and use of supplements. RESULTS: Among patients with a diagnosis based on serology results, 33.3% were diagnosed by non-gastroenterologists vs 20.7% in the biopsy diagnosed group (P < .001). Fewer patients with a diagnosis based on serology results sought nutritional counseling at the time of diagnosis (40.1%) than patients with a diagnosis based on biopsy (58.9%) (P < .001). A higher proportion of patients diagnosed by serology without biopsy took dietary supplements to aid in digestion of gluten (19.8%) than patients with a diagnosis based on biopsy (8.9%) (P < .001). After we adjusted for age and sex, patients with a diagnosis based on serology were less likely to seek nutritional counseling after diagnosis (odds ratio [OR], 0.45; 95% CI, 0.33-0.63), less likely to receive a diagnosis from a gastroenterologist (OR, 0.16; 95% CI, 0.07-0.37), and more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19). CONCLUSIONS: In an analysis of data from a PPRN, we found that 21% of adult participants with celiac disease did not have a diagnosis based on a duodenal biopsy. Patients with a diagnosis based on serology results were more likely to be diagnosed by non-gastroenterologists, less likely to seek nutritional counseling, and more likely to use dietary supplements. Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation of their disease.

7 Article High Frequency of Extractable Nuclear Autoantibodies in Wheat-Related Disorders. 2018

Yang, Yuanyuan / Krishna, Karthik / Deshpande, Payal / Ranganathan, Vinodh / Jayaraman, Vasanth / Wang, Tianhao / Bei, Kang / Krishnamurthy, Hari. ·Vibrant America LLC, San Carlos, CA, USA. · Vibrant Sciences LLC, San Carlos, CA, USA. ·Biomark Insights · Pubmed #29977112.

ABSTRACT: Background and aims: There has been broad interest to explore the presence of autoimmunity among wheat-sensitive individuals, but neither the pathogenesis nor the relevance has been established. In this study, we evaluated the frequencies and levels of autoantibodies, which are important biomarkers of autoimmunity, in subjects with wheat-related disorders and controls. Anti-nuclear antibodies (ANA) and the specific ones against extractable nuclear antigens (ENA) were investigated. Methods: A total of 713 subjects who showed symptoms related to wheat ingestion were addressed to Vibrant America Clinical Laboratory from December 2015 to November 2017. Serum samples were collected from all subjects and tested with a wheat protein antibody panel (IgG and IgA to 18 proteins at the peptide level) and an autoantibody panel (ANA by immunofluorescence analysis and 10 ENA antibodies). Retrospective analysis was completed using de-identified clinical data and test results. Results: In the retrospective analysis, 38 (5%) were seropositive in a Celiac Disease panel, 491 (83%) were seropositive in a wheat protein antibody panel "Wheat Zoomer," and 84 (12%) were seronegative in both panels. Anti-nuclear antibodies were detected in similar portions of the celiac disease subjects (13%), the Wheat Zoomer-positive subjects (12%), and seronegative controls (15%), which is also very close to the reported occurrence of ANA positivity (15%) in the healthy population. The prevalence of anti-ENA was reported to be less than 2% in the general population; however, our study found it to be much higher in the celiac disease subjects (29%) and the wheat-sensitive subjects (27%), compared with a smaller proportion of seronegative controls (19%). The prevalence of anti-histone was especially prominent among the celiac disease subjects (73%) and the Wheat Zoomer-positive subjects (60%). Conclusions: High proportions of wheat-related disease subjects carry ENA antibodies that are important specific biomarkers of autoimmunity.

8 Article The Effect of Depressive Symptoms on the Association between Gluten-Free Diet Adherence and Symptoms in Celiac Disease: Analysis of a Patient Powered Research Network. 2018

Joelson, Andrew M / Geller, Marilyn G / Zylberberg, Haley M / Green, Peter H R / Lebwohl, Benjamin. ·Department of Internal Medicine, New York Presbyterian Hospital, New York, NY 10032, USA. amj9033@nyp.org. · Celiac Disease Foundation, Woodland Hills, CA 91364, USA. marilyn.geller@celiac.org. · Celiac Disease Center, Department of Medicine, Columbia University Medical Center, 180 Fort Washington Avenue, Suite 936, New York, NY 10032, USA. hmz2105@columbia.edu. · Celiac Disease Center, Department of Medicine, Columbia University Medical Center, 180 Fort Washington Avenue, Suite 936, New York, NY 10032, USA. pg11@cumc.columbia.edu. · Celiac Disease Center, Department of Medicine, Columbia University Medical Center, 180 Fort Washington Avenue, Suite 936, New York, NY 10032, USA. BL114@columbia.edu. · Deartment of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USA. BL114@columbia.edu. ·Nutrients · Pubmed #29701659.

ABSTRACT: BACKGROUND: The prevalence of depression in celiac disease (CD) is high, and patients are often burdened socially and financially by a gluten-free diet. However, the relationship between depression, somatic symptoms and dietary adherence in CD is complex and poorly understood. We used a patient powered research network (iCureCeliac METHODS: We identified patients with biopsy-diagnosed celiac disease who answered questions pertaining to symptoms (Celiac Symptom Index (CSI)), GFD adherence (Celiac Dietary Adherence Test (CDAT)), and a 5-point, scaled question regarding depressive symptoms relating to patients' celiac disease. We then measured the correlation between symptoms and adherence (CSI vs. CDAT) in patients with depression versus those without depression. We also tested for interaction of depression with regard to the association with symptoms using a multiple linear regression model. RESULTS: Among 519 patients, 86% were female and the mean age was 40.9 years. 46% of patients indicated that they felt "somewhat," "quite a bit," or "very much" depressed because of their disorder. There was a moderate correlation between worsened celiac symptoms and poorer GFD adherence ( CONCLUSIONS: In patients with depressive symptoms related to their disorder, correlation between adherence and symptoms was weaker than those without depressive symptoms. This finding was confirmed with a linear regression analysis, showing that depressive symptoms may modify the effect of a GFD on celiac symptoms. Depressive symptoms may therefore mask the relationship between inadvertent gluten exposure and symptoms. Additional longitudinal and prospective studies are needed to further explore this potentially important finding.

9 Article A B-Cell Gene Signature Correlates With the Extent of Gluten-Induced Intestinal Injury in Celiac Disease. 2017

Garber, Mitchell E / Saldanha, Alok / Parker, Joel S / Jones, Wendell D / Kaukinen, Katri / Laurila, Kaija / Lähdeaho, Marja-Leena / Khatri, Purvesh / Khosla, Chaitan / Adelman, Daniel C / Mäki, Markku. ·Alvine Pharmaceuticals, Inc, San Carlos, California. · Department of Chemistry, Stanford, California. · InterSystems Corporation, Cambridge, Massachusetts. · Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. · Department of Genetics, University of North Carolina, Chapel Hill, North Carolina. · EA Genomics, Division of Q Solutions, Morrisville, North Carolina. · University of Tampere Faculty of Medicine and Life Sciences, Tampere, Finland. · Department of Internal Medicine, Tampere, Finland. · Tampere University Hospital, Tampere, Finland. · Department of Pediatrics, Tampere, Finland. · Institute for Immunity, Transplantation and Infection, Stanford, California. · Division of Biomedical Informatics, Department of Medicine, Stanford, California. · Department of Chemical Engineering, Stanford, California. · Stanford ChEM-H, Stanford University, Stanford, California. · Division of Allergy/Immunology, Department of Medicine, University of California San Francisco, San Francisco, California. · Tampere Center for Child Health Research, Tampere, Finland. ·Cell Mol Gastroenterol Hepatol · Pubmed #28508029.

ABSTRACT: BACKGROUND & AIMS: Celiac disease (CeD) provides an opportunity to study autoimmunity and the transition in immune cells as dietary gluten induces small intestinal lesions. METHODS: Seventy-three celiac disease patients on a long-term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A peripheral blood sample and intestinal biopsy specimens were taken before and 6 weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus-height-to-crypt-depth ratio to quantify gluten-induced intestinal injury. Pooled B and T cells were isolated from whole blood, and RNA was analyzed by DNA microarray looking for changes in peripheral B- and T-cell gene expression that correlated with changes in villus height to crypt depth, as patients maintained a relatively healthy intestinal mucosa or deteriorated in the face of a gluten challenge. RESULTS: Gluten-dependent intestinal damage from baseline to 6 weeks varied widely across all patients, ranging from no change to extensive damage. Genes differentially expressed in B cells correlated strongly with the extent of intestinal damage. A relative increase in B-cell gene expression correlated with a lack of sensitivity to gluten whereas their relative decrease correlated with gluten-induced mucosal injury. A core B-cell gene module, representing a subset of B-cell genes analyzed, accounted for the correlation with intestinal injury. CONCLUSIONS: Genes comprising the core B-cell module showed a net increase in expression from baseline to 6 weeks in patients with little to no intestinal damage, suggesting that these individuals may have mounted a B-cell immune response to maintain mucosal homeostasis and circumvent inflammation. DNA microarray data were deposited at the GEO repository (accession number: GSE87629; available: https://www.ncbi.nlm.nih.gov/geo/).

10 Article A Novel Patient-Derived Conceptual Model of the Impact of Celiac Disease in Adults: Implications for Patient-Reported Outcome and Health-Related Quality-of-Life Instrument Development. 2017

Leffler, Daniel A / Acaster, Sarah / Gallop, Katy / Dennis, Melinda / Kelly, Ciarán P / Adelman, Daniel C. ·Celiac Center, Beth Israel Deaconess Medical Center, Boston, MA, USA; Celiac Research Program, Harvard Medical School, Boston, MA, USA. Electronic address: dleffler@bidmc.harvard.edu. · Acaster Consulting Ltd., London, UK. · Celiac Center, Beth Israel Deaconess Medical Center, Boston, MA, USA; Celiac Research Program, Harvard Medical School, Boston, MA, USA. · Alvine Pharmaceuticals, Inc., San Carlos, CA, USA. ·Value Health · Pubmed #28408006.

ABSTRACT: BACKGROUND: Celiac disease is a chronic inflammatory condition with wide ranging effects on individual's lives caused by a combination of symptoms and the burden of adhering to a gluten-free diet (GFD). OBJECTIVES: To further understand patients' experience of celiac disease, the impact it has on health-related quality of life (HRQOL), and to develop a conceptual model describing this impact. METHODS: Adults with celiac disease on a GFD reporting symptoms within the previous 3 months were included; patients with refractory celiac disease and confounding medical conditions were excluded. A semistructured discussion guide was developed exploring celiac disease symptoms and impact on patients' HRQOL. An experienced interviewer conducted in-depth interviews. The data set was coded and analyzed using thematic analysis to identify concepts, themes, and the inter-relationships between them. Data saturation was monitored and concepts identified formed the basis of the conceptual model. RESULTS: Twenty-one participants were recruited, and 32 distinct gluten-related symptoms were reported and data saturation was reached. Analysis identified several themes impacting patients' HRQOL: fears and anxiety, day-to-day management of celiac disease, physical functioning, sleep, daily activities, social activities, emotional functioning, and relationships. The conceptual model highlights the main areas of impact and the relationships between concepts. CONCLUSIONS: Both symptoms and maintaining a GFD have a substantial impact on patient functioning and HRQOL in adults with celiac disease. The conceptual model derived from these data may help to design future patient-reported outcomes as well as interventions to improve the quality of life in an individual with celiac disease.

11 Article Direct Costs in Patients with Celiac Disease in the USA: A Retrospective Claims Analysis. 2016

Guandalini, Stefano / Tundia, Namita / Thakkar, Roopal / Macaulay, Dendy / Essenmacher, Kirk / Fuldeore, Mahesh. ·University of Chicago, 5721 S. Maryland Avenue, Chicago, IL, 60637, USA. sguandalini@peds.bsd.uchicago.edu. · AbbVie Inc., 1 N Waukegan Road, North Chicago, IL, 60064, USA. · Analysis Group, 10 Rockefeller Plaza, 15th Floor, New York, NY, 10020, USA. · Alvine Pharmaceuticals, 75 Shoreway Road, Suite B, San Carlos, CA, 94070, USA. ·Dig Dis Sci · Pubmed #27417565.

ABSTRACT: BACKGROUND: Celiac disease (CeD) is an autoimmune disease triggered by gluten ingestion. AIM: We assessed total direct costs burden associated with CeD in patients with CeD versus patients without CeD using administrative claims data. METHODS: Patients with CeD (cases) with ≥1 occurrences of CeD diagnosis were selected at a randomly chosen date (index date) from the OptumHealth Reporting and Insights database from 01/01/1998 through 03/31/2013. Cases were continuously enrolled throughout baseline (1 year before index date) and study (1 year after index date) periods. Cases were categorized as full remission and partial remission and matched 1:1 based on age, sex, region, index date, company, and employment status. Total all-cause and CeD-related costs were calculated. RESULTS: A total of 12,187 cases were matched with an equal number of controls. Mean total all-cause costs were $12,217 in cases versus $4935 in controls (P < 0.0001). In full remission (N = 10,181 [83.5 %]) and partial remission (N = 2006 [16.5 %]) cases, mean total all-cause direct costs (cases versus controls) were $11,038 versus $4962 and $18,206 versus $4796, respectively. All-cause medical costs ($9839 for all cases, $8723 for full remission cases, $15,499 for partial remission cases) accounted for the majority of all-cause total costs and included outpatient costs ($6675; $6456; and $7785, respectively) and hospitalizations ($2776; $1963; and $6906, respectively). CeD-related medical costs were 13 and 27 % of all-cause medical costs for all cases and partial remission cases, respectively. CONCLUSIONS: Patients with CeD and partial remission of CeD incurred significantly higher (2.5 and 3.8 times) total all-cause costs compared with matched controls.

12 Article Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays. 2016

Choung, Rok Seon / Marietta, Eric V / Van Dyke, Carol T / Brantner, Tricia L / Rajasekaran, John / Pasricha, Pankaj J / Wang, Tianhao / Bei, Kang / Krishna, Karthik / Krishnamurthy, Hari K / Snyder, Melissa R / Jayaraman, Vasanth / Murray, Joseph A. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States of America. · Vibrant Sciences LLC, San Carlos, CA, United States of America. · Center for Neurogastroenterology, Johns Hopkins University, Baltimore, MD, United States of America. · Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, MN, United States of America. ·PLoS One · Pubmed #26824466.

ABSTRACT: BACKGROUND: Most antibodies recognize conformational or discontinuous epitopes that have a specific 3-dimensional shape; however, determination of discontinuous B-cell epitopes is a major challenge in bioscience. Moreover, the current methods for identifying peptide epitopes often involve laborious, high-cost peptide screening programs. Here, we present a novel microarray method for identifying discontinuous B-cell epitopes in celiac disease (CD) by using a silicon-based peptide array and computational methods. METHODS: Using a novel silicon-based microarray platform with a multi-pillar chip, overlapping 12-mer peptide sequences of all native and deamidated gliadins, which are known to trigger CD, were synthesized in situ and used to identify peptide epitopes. RESULTS: Using a computational algorithm that considered disease specificity of peptide sequences, 2 distinct epitope sets were identified. Further, by combining the most discriminative 3-mer gliadin sequences with randomly interpolated3- or 6-mer peptide sequences, novel discontinuous epitopes were identified and further optimized to maximize disease discrimination. The final discontinuous epitope sets were tested in a confirmatory cohort of CD patients and controls, yielding 99% sensitivity and 100% specificity. CONCLUSIONS: These novel sets of epitopes derived from gliadin have a high degree of accuracy in differentiating CD from controls, compared with standard serologic tests. The method of ultra-high-density peptide microarray described here would be broadly useful to develop high-fidelity diagnostic tests and explore pathogenesis.

13 Article Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. 2014

Lähdeaho, Marja-Leena / Kaukinen, Katri / Laurila, Kaija / Vuotikka, Pekka / Koivurova, Olli-Pekka / Kärjä-Lahdensuu, Tiina / Marcantonio, Annette / Adelman, Daniel C / Mäki, Markku. ·School of Medicine, University of Tampere, Tampere University Hospital, Tampere, Finland. · Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland; Department of Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland. · Liikuntaklinikka, Oulu Diakonissalaitos, Oulu, Finland. · Terveys, Oulu Diakonissalaitos, Oulu, Finland. · FinnMedi Oy, Tampere, Finland. · Alvine Pharmaceuticals, Inc., San Carlos, California. · Alvine Pharmaceuticals, Inc., San Carlos, California. Electronic address: dadelman@alvinepharma.com. ·Gastroenterology · Pubmed #24583059.

ABSTRACT: BACKGROUND & AIMS: Gluten ingestion leads to small intestinal mucosal injury in patients with celiac disease, necessitating strict life-long exclusion of dietary gluten. Despite adherence to a gluten-free diet, many patients remain symptomatic and still have small intestinal inflammation. In this case, nondietary therapies are needed. We investigated the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases given orally, to protect patients with celiac disease from gluten-induced mucosal injury in a phase 2 trial. METHODS: We established the optimal daily dose of gluten to be used in a 6-week challenge study. Then, in the intervention study, adults with biopsy-proven celiac disease were randomly assigned to groups given ALV003 (n = 20) or placebo (n = 21) together with the daily gluten challenge. Duodenal biopsies were collected at baseline and after gluten challenge. The ratio of villus height to crypt depth and densities of intraepithelial lymphocytes were the primary end points. RESULTS: A daily dose of 2 g gluten was selected for the intervention study. Sixteen patients given ALV003 and 18 given placebo were eligible for efficacy evaluation. Biopsies from subjects in the placebo group showed evidence of mucosal injury after gluten challenge (mean villus height to crypt depth ratio changed from 2.8 before challenge to 2.0 afterward; P = .0007; density of CD3(+) intraepithelial lymphocytes changed from 61 to 91 cells/mm after challenge; P = .0003). However, no significant mucosal deterioration was observed in biopsies from the ALV003 group. Between groups, morphologic changes and CD3(+) intraepithelial lymphocyte counts differed significantly from baseline to week 6 (P = .0133 and P = .0123, respectively). There were no statistically significant differences in symptoms between groups. CONCLUSIONS: Based on a phase 2 trial, the glutenase ALV003 appears to attenuate gluten-induced small intestinal mucosal injury in patients with celiac disease in the context of an everyday gluten-free diet containing daily up to 2 g gluten. Clinicaltrial.gov, NUMBERS: NCT00959114 and NCT01255696.

14 Minor Prevalence of HLA-DQ2 and DQ8 haplotypes that predispose to celiac disease in Mexico. 2019

Mejía-León, M E / Calderón-de la Barca, A M. ·Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Mexicali, Baja California, México. · Coordinación de Nutrición, Centro de Investigación en Alimentación y Desarrollo, A.C., Hermosillo, Sonora, México. Electronic address: amc@ciad.mx. ·Rev Gastroenterol Mex · Pubmed #30119968.

ABSTRACT: -- No abstract --