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https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#1
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28878121/a-tcr%C3%AE-framework-centered-codon-shapes-a-biased-t-cell-repertoire-through-direct-mhc-and-cdr3%C3%AE-interactions
#2
Kristin Støen Gunnarsen, Lene Støkken Høydahl, Louise Fremgaard Risnes, Shiva Dahal-Koirala, Ralf Stefan Neumann, Elin Bergseng, Terje Frigstad, Rahel Frick, M Fleur du Pré, Bjørn Dalhus, Knut Ea Lundin, Shuo-Wang Qiao, Ludvig M Sollid, Inger Sandlie, Geir Åge Løset
Selection of biased T cell receptor (TCR) repertoires across individuals is seen in both infectious diseases and autoimmunity, but the underlying molecular basis leading to these shared repertoires remains unclear. Celiac disease (CD) occurs primarily in HLA-DQ2.5+ individuals and is characterized by a CD4+ T cell response against gluten epitopes dominated by DQ2.5-glia-α1a and DQ2.5-glia-α2. The DQ2.5-glia-α2 response recruits a highly biased TCR repertoire composed of TRAV26-1 paired with TRBV7-2 harboring a semipublic CDR3β loop...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28828296/cardiometabolic-risk-factors-in-children-with-celiac-disease-on-a-gluten-free-diet
#3
REVIEW
Caterina Anania, Lucia Pacifico, Francesca Olivero, Francesco Massimo Perla, Claudio Chiesa
Celiac disease (CD) is an immune-mediated systemic condition evoked by gluten and related prolamines in genetically predisposed subjects. It is characterised by a variable combination of gluten-dependent clinical symptoms, CD-specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. The only therapy of CD consists of a life-long gluten free diet (GFD). Strict GFD adherence results in full clinical, serological and histological remission, avoiding long-term complications in CD patients. However, this diet is not without problems...
August 8, 2017: World Journal of Clinical Pediatrics
https://www.readbyqxmd.com/read/28819290/progress-towards-non-invasive-diagnosis-and-follow-up-of-celiac-disease-in-children-a-prospective-multicentre-study-to-the-usefulness-of-plasma-i-fabp
#4
M P M Adriaanse, A Mubarak, R G Riedl, F J W Ten Kate, J G M C Damoiseaux, W A Buurman, R H J Houwen, A C E Vreugdenhil
This prospective study investigates whether measurement of plasma intestinal-fatty acid binding protein (I-FABP), a sensitive marker for small intestinal epithelial damage, improves non-invasive diagnosing of celiac disease (CD), and whether I-FABP levels are useful to evaluate mucosal healing in patients on a gluten-free diet (GFD). Ninety children with elevated tTG-IgA titres and HLA-DQ2/DQ8 positivity were included (study group). Duodenal biopsies were taken, except in those fulfilling the ESPGHAN criteria...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810029/celiac-disease-and-nonceliac-gluten-sensitivity-a-review
#5
REVIEW
Maureen M Leonard, Anna Sapone, Carlo Catassi, Alessio Fasano
Importance: The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Observations: Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial)...
August 15, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28797308/coeliac-disease-in-infants-antibodies-to-deamidated-gliadin-peptide-come-first
#6
Michele Arigliani, Francesca Rech Morassutti, Martina Fabris, Paola Melli, Elio Tonutti, Paola Cogo
BACKGROUND: The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD. CASE PRESENTATION: We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay...
August 10, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28761890/microscopic-colitis-after-fecal-microbiota-transplant
#7
Matthew J Fasullo, Yasir Al-Azzawi, Jeffrey Abergel
Microscopic colitis (MC) is an inflammatory condition of the large bowel that is associated with chronic, nonbloody diarrhea. Colonoscopy usually demonstrates normal mucosa, while tissue biopsy reveals intraepithelial lymphocytes or a subepithelial collagen band. Although no specific antibody has been discovered, MC is associated with several autoimmune disorders such as celiac disease, Hashimoto's thyroiditis, and rheumatoid arthritis. There are only a small number of case reports documenting possible hereditary MC cases, but up to 12% of patients with MC have a family history of inflammatory bowel disease...
2017: ACG Case Reports Journal
https://www.readbyqxmd.com/read/28709446/omitting-duodenal-biopsy-in-children-with-suspected-celiac-disease-and-extra-intestinal-symptoms
#8
Mauro Bozzola, Cristina Meazza, Chiara Gertosio, Sara Pagani, Daniela Larizza, Valeria Calcaterra, Ombretta Luinetti, Giovanni Farello, Carmine Tinelli, Lorenzo Iughetti
BACKGROUND: The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines. METHODS: In this retrospective study a total of 105 patients, suspected of having CD because of extra-intestinal symptoms and showing serum tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) measurements and HLA genotyping, were considered for the final analysis (33 boys and 72 girls; age range 1...
July 15, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28701370/twenty-year-progression-rate-to-clinical-onset-according-to-autoantibody-profile-age-and-hla-dq-genotype-in-a-registry-based-group-of-children-and-adults-with-a-first-degree-relative-with-type-1-diabetes
#9
Frans K Gorus, Eric V Balti, Anissa Messaaoui, Simke Demeester, Annelien Van Dalem, Olivier Costa, Harry Dorchy, Chantal Mathieu, Luc Van Gaal, Bart Keymeulen, Daniël G Pipeleers, Ilse Weets
OBJECTIVE: We investigated whether islet autoantibody profile, HLA-DQ genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb(+)) in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Persistently islet autoAb(+) siblings and offspring (n = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28638585/clinicopathological-study-of-seronegative-celiac-disease-in-adults-in-pakistan-a-pilot-study
#10
Mohammad Hanif Farina, Rajesh Kumar Mandhwani, Nasir Hassan Luck, Zaigham Abbas, Muhammed Mubarak, S Mudassir Laeeq, Abbas Ali Tasneem
BACKGROUND Celiac disease (CD) is usually missed, if the serology is negative. We aimed to evaluate the clinicopathological characteristics of seronegative CD (SNCD) and its response to gluten-free diet (GFD) in adult patients. METHODS This observational study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from 2009 to 2015. All consecutive adult patients (≥17 years) with features of marked villous atrophy (Marsh class≥III) on duodenal biopsy, negative tissue transglutaminase IgA and IgG antibodies (anti-tTg IgA and IgG) and human leukocyte antigen (HLA) DQ2 or DQ8 serotypes were studied...
April 2017: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28624578/accuracy-in-diagnosis-of-celiac-disease-without-biopsies-in%C3%A2-clinical-practice
#11
Katharina J Werkstetter, Ilma R Korponay-Szabó, Alina Popp, Vincenzo Villanacci, Marianna Salemme, Gabriele Heilig, Søren Thue Lillevang, Maria Luisa Mearin, Carmen Ribes-Koninckx, Adrian Thomas, Riccardo Troncone, Birgit Filipiak, Markku Mäki, Judit Gyimesi, Mehri Najafi, Jernej Dolinšek, Stine Dydensborg Sander, Renata Auricchio, Alexandra Papadopoulou, Andreas Vécsei, Peter Szitanyi, Ester Donat, Rafaella Nenna, Philippe Alliet, Francesca Penagini, Hélène Garnier-Lengliné, Gemma Castillejo, Kalle Kurppa, Ranaan Shamir, Almuthe Christine Hauer, Françoise Smets, Susana Corujeira, Myriam van Winckel, Stefan Buderus, Sonny Chong, Steffen Husby, Sibylle Koletzko
BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28566880/immune-response-to-vaccines-in-children-with-celiac-disease
#12
EDITORIAL
Caterina Anania, Francesca Olivero, Alessandra Spagnolo, Claudio Chiesa, Lucia Pacifico
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28535873/similar-responses-of-intestinal-t-cells-from-untreated-children-and-adults-with-celiac-disease-to-deamidated-gluten-epitopes
#13
MULTICENTER STUDY
Melinda Ráki, Shiva Dahal-Koirala, Hao Yu, Ilma R Korponay-Szabó, Judit Gyimesi, Gemma Castillejo, Jørgen Jahnsen, Shuo-Wang Qiao, Ludvig M Sollid
BACKGROUND & AIMS: Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides...
September 2017: Gastroenterology
https://www.readbyqxmd.com/read/28514313/clinical-and-biological-correlations-in-celiac-disease-in-children-the-prospective-single-experience-of-a-romanian-tertiary-center-a-case-control-study-strobe-compliant-study
#14
Cristina Oana Marginean, Lorena Elena Meliţ, Roxana-Cristina Mareş, Maria Oana Mărginean, Septimiu Voidăzan, Minodora Dobreanu
Celiac disease-a chronic inflammatory disease of the intestine-is triggered by gluten or associated protein consumption.The aim of our study was to assess the sensitivity, specificity of the combined anti-transglutaminase 2 (TG2)/deamidated gliadin peptide antibodies (DGP), and antiendomisium antibodies (EMA), to determine the distribution of HLA-DQ2/DQ8 for the 140 tested patients, and also to evaluate the clinical and laboratory characteristics of patients admitted with the suspicion of celiac disease (CD)...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28506538/epitope-specific-immunotherapy-targeting-cd4-positive-t-cells-in-coeliac-disease-two-randomised-double-blind-placebo-controlled-phase-1-studies
#15
Gautam Goel, Tim King, A James Daveson, Jane M Andrews, Janakan Krishnarajah, Richard Krause, Gregor J E Brown, Ronald Fogel, Charles F Barish, Roger Epstein, Timothy P Kinney, Philip B Miner, Jason A Tye-Din, Adam Girardin, Juha Taavela, Alina Popp, John Sidney, Markku Mäki, Kaela E Goldstein, Patrick H Griffin, Suyue Wang, John L Dzuris, Leslie J Williams, Alessandro Sette, Ramnik J Xavier, Ludvig M Sollid, Bana Jabri, Robert P Anderson
BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet...
May 11, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28483757/barriers-to-implementing-the-revised-espghan-guidelines-for-coeliac-disease-in-children-a-cross-sectional-survey-of-coeliac-screen-reporting-in-laboratories-in-england
#16
Siba Prosad Paul, Sophie Louise Harries, Dharamveer Basude
BACKGROUND: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing paediatric coeliac disease (CD) were revised in 2012. This enabled serological diagnosis in a selective group of symptomatic children using anti-tissue transglutaminase (anti-tTG) titre, antiendomysial antibodies (EMA) and HLA DQ2/DQ8 status. However, observing variations in the availability of serological tests for CD within our region, we conducted a countrywide survey to explore the diversity of these tests for all paediatric centres...
May 8, 2017: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/28456719/abnormalities-in-cd57-cytotoxic-t-cells-and-v%C3%AE-1-%C3%AE-%C3%AE-t-cells-in-subclinical-celiac-disease-in-childhood-are-affected-by-cytomegalovirus-the-generation-r-study
#17
M A E Jansen, D van den Heuvel, V W V Jaddoe, M C van Zelm, H A Moll
Celiac disease (CD) is a digestive and autoimmune disorder driven by an immune response to modified gluten peptides. Affected intestines show infiltrates of various T-cell and NK-cell subsets. It is currently unclear if individuals with subclinical CD have systemic abnormalities in immune cells. We here studied whether subclinical CD is associated with changes in blood CD57-expressing and Vδ1-expressing lymphocytes in children, and whether cytomegalovirus (CMV) infection modifies this association. Included were 1068 children from the Generation R Study...
April 26, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28433781/prevalence-of-celiac-disease-autoimmunity-among-adolescents-and-young-adults-in-china
#18
Juanli Yuan, Chunyan Zhou, Jinyan Gao, Jingjing Li, Fenglian Yu, Jun Lu, Xin Li, Xiaozhong Wang, Ping Tong, Zhihua Wu, Anshu Yang, Yonghong Yao, Sarah Nadif, Heng Shu, Xu Jiang, Yujie Wu, Luud Gilissen, Hongbing Chen
BACKGROUND & AIMS: In China, epidemiologic information on celiac disease autoimmunity is scarce and fragmented. We investigated the prevalence of celiac disease autoimmunity in the general Chinese population. METHODS: In a cross-sectional prospective study, 19,778 undiagnosed Chinese adolescents and young adults (age, 16-25 y) were recruited from consecutive new students who underwent routine physical examinations at 2 universities in Jiangxi, China, from September 2010 through October 2013; the students were from 27 geographic regions in China...
April 19, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28387454/coeliac-disease-and-gastrointestinal-symptom-screening-in-adult-first-degree-relatives
#19
Luis Vaquero, Laura Rodríguez-Martín, Begoña Alvarez-Cuenllas, Mercedes Hernando, Cristina Iglesias-Blazquez, Cristina Menéndez-Arias, Santiago Vivas
BACKGROUND AND AIM: The first-degree relatives (FDRs) of patients with coeliac disease are the main risk group for disease development. To evaluate the screening strategy in FDRs with negative coeliac serology based on human leukocyte antigen (HLA) genotyping, followed by duodenal biopsy, and to analyze the prevalence of gastrointestinal symptoms and the influence of gluten intake. METHODS: Adult FDRs with negative coeliac serology were invited to participate (n = 205), and a total of 139 completed the study protocol...
April 7, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28364043/unraveling-the-structural-basis-for-the-unusually-rich-association-of-human-leukocyte-antigen-dq2-5-with-class-ii-associated-invariant-chain-peptides
#20
Thanh-Binh Nguyen, Priya Jayaraman, Elin Bergseng, M S Madhusudhan, Chu-Young Kim, Ludvig M Sollid
Human leukocyte antigen (HLA)-DQ2.5 (DQA1*05/DQB1*02) is a class-II major histocompatibility complex protein associated with both type 1 diabetes and celiac disease. One unusual feature of DQ2.5 is its high class-II-associated invariant chain peptide (CLIP) content. Moreover, HLA-DQ2.5 preferentially binds the non-canonical CLIP2 over the canonical CLIP1. To better understand the structural basis of HLA-DQ2.5's unusual CLIP association characteristics, better insight into the HLA-DQ2.5·CLIP complex structures is required...
June 2, 2017: Journal of Biological Chemistry
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