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    Children with Celiac Disease Have Different Genetic Signatures than Adults


    Jefferson Adams

    Celiac.com 03/02/2016 - A team of researchers recently completed the first extensive study comparing gene expression in children and adults with celiac disease, and found some key differences between the two groups.


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    Photo: CC--Nicolas BufflerThe research team included V. Pascual, L. M. Medrano , N. López-Palacios, A. Bodas, B. Dema, M. Fernández-Arquero, B. González-Pérez, I. Salazar, and C. Núñez. They are variously affiliated with Servicio de Pediatría, Servicio de Aparato Digestivo, and Servicio de Inmunología Clínica at the Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, and with the Departamento de Producción Animal, Facultad de Veterinaria, and the Departamento de Estadística e Investigación Operativa I, Facultad de Matemáticas, Universidad Complutense de Madrid in Madrid, Spain.

    For their study, the team collected 19 duodenal biopsies of children and adults with celiac disease and compared the expression of 38 selected genes between each other, and in 13 non-celiac disease control subjects matched by age.

    The team used a Baysian methodology to analyze the differences of gene expression between groups. They found that, compared to controls, children and adults with celiac disease all had seven genes with a similarly altered expression. These were C2orf74, CCR6, FASLG, JAK2, IL23A, TAGAP and UBE2L3.

    The team found differences in 13 genes, six of which were altered only in adults (IL1RL1, celiac disease28, STAT3, TMEM187, VAMP3 and ZFP36L1) and two only in children (TNFSF18 and ICOSLG); while four genes show a significantly higher alteration in adults (CCR4, IL6, IL18RAP and PLEK) and one in children (C1orf106).

    Between the two groups, the team found significant differences in the expression level of several genes, most notably the higher alteration seen in adults.

    The team is calling for further research to assess possible genetic influences behind the changes, along with the specific physical consequences of the reported differences.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Celiac.com 02/18/2015 - It's well documented that HLA-DQ molecules play a role in the pathogenesis of celiac disease through the presentation of gluten peptides to CD4(+) T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease.
    Researchers have recently showed that T cells of DQ2.5 and DQ2.2 patients recognize distinct sets of gluten epitopes, which indicates that these two DQ2 variants select different peptides for display.
    To figure out if this is the case, the research team performed a comprehensive comparison of the endogenous self-peptides bound to HLA-DQ molecules of B-lymphoblastoid cell lines. The research team included E. Bergseng, S. Dørum, M. Arntzen, M. Nielsen, S. Nygård, S. Buus, G.A. de Souza, and L.M. Sollid. They are variously affiliated with the Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
    The team began by isolating peptides from affinity-purified HLA molecules of nine cell lines. They then subjected the isolated peptides to quadrupole orbitrap mass spectrometry and MaxQuant software analysis. They identified 12,712 endogenous peptides at very different relative abundances. Hierarchical clustering of normalized quantitative data revealed significant differences in repertoires of peptides between the three DQ variant molecules.
    They identified peptide-binding motifs using the neural network-based method, NNAlign. The binding motifs of DQ2.5 and DQ7.5 concurred with previously established binding motifs, but the binding motif of DQ2.2 was remarkably different from that of DQ2.5, with position, P3 being a major anchor having a preference for threonine and serine.
    This is interesting for the reason that three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine at position P3.
    This study shows that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules can provide clues to understand HLA association with disease.
    Source:
    Immunogenetics. 2015 Feb;67(2):73-84. doi: 10.1007/s00251-014-0819-9. Epub 2014 Dec 12.

    Jefferson Adams
    Celiac.com 06/03/2015 - Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region.
    A team of researchers recently set out to fine map the MHC association signal to identify additional celiac disease risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles. The researchers included J. Gutierrez-Achury, A. Zhernakova, S.L. Pulit, G. Trynka, K.A. Hunt, J. Romanos, S. Raychaudhuri, D.A. van Heel, C. Wijmenga, and P.I. de Bakker.
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    Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.
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    Research team members are variously affiliated with the Department of Genetics, University Medical Center, University of Groningen, Groningen, the Netherlands, the Department of Medical Genetics at the Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands, the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK, the Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, the Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, the Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, the Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK, the Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands, and with the Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
    Source:
    Nat Genet. 2015 Apr 20. doi: 10.1038/ng.3268.

    Jefferson Adams
    Celiac.com 09/16/2015 - Autoimmune disease, such as type 1 diabetes, Crohn's disease, and juvenile idiopathic arthritis, affect about 7 to 10 percent of the population in the Western Hemisphere.
    Using genome-wide association studies (GWASs), researchers have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases.
    A team of researchers recently conducted an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls.
    The research team included Yun R Li, Jin Li, Sihai D Zhao, Jonathan P Bradfield, Frank D Mentch, S Melkorka Maggadottir, Cuiping Hou, Debra J Abrams, Diana Chang, Feng Gao, Yiran Guo, Zhi Wei, John J Connolly, Christopher J Cardinale, Marina Bakay, Joseph T Glessner, Dong Li, Charlly Kao, Kelly A Thomas, Haijun Qiu, Rosetta M Chiavacci, Cecilia E Kim, Fengxiang Wang, James Snyder, and Marylyn D Richie.
    The are variously affiliated with The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; the Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; the Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; the Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA; the Program in Computational Biology and Medicine, Cornell University, Ithaca, New York, USA, and the Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA.
    For their study, the team identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG.
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    Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases.

    Source:
    Nature Medicine 21, 1018–1027 (2015) doi:10.1038/nm.3933

    Jefferson Adams
    Celiac.com 12/14/2015 - Recently, several studies have set out to determine how intake of gluten during infancy influences later risk of celiac disease.
    One such study, conducted in Sweden, investigated whether gluten intake before 2 years of age increases the risk for celiac disease in genetically susceptible children. The research team included Carin Andrén Aronsson, Hye-Seung Lee, Sibylle Koletzko, Ulla Uusitalo, Jimin Yang, Suvi M. Virtanen, Edwin Liu, Åke Lernmark, Jill M. Norris, and Daniel Agardh.
    They are variously affiliated with the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado, the Department of Epidemiology, Colorado School of Public Campus, University of Colorado Denver in Aurora, Colorado, the Department of Clinical Sciences at Lund University and Skåne University Hospital in Malmö, Sweden, with Dr. von Hauner Children's Hospital, Ludwig Maximilians University in Munich, Germany, the National Institute for Health and Welfare, Nutrition Unit in Helsinki, Finland, the School of Health Sciences, University of Tampere, Finland, the Research Center for Child Health, Tampere University and University Hospital, Science Center of Pirkanmaa Hospital District, University of Tampere, Finland, and with the Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida.
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    The results showed that the duration of breastfeeding, lasting 32 weeks, on average, and average age at first introduction to gluten of 22 weeks was basically the same for the target group and the tTGA-negative control group.
    At the visit prior to tTGA seroconversion, the target group reported a larger intake of gluten, 4.9 grams a day, compared to 3.9 grams a day for controls (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13–1.46; P = .0002).
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    These findings may be taken into account for future infant feeding recommendations. So, basically, if kids have a genetic susceptibility to celiac disease, regardless of their genetic haplotypes, then parents should wait until after 2 yearss of age to introduce gluten into the child's diet.
    This study, taken together with another recent study that shows that introduction of gluten after six months of age might promote an increased risk of celiac disease, might help provide some guidance for parents looking to introduce gluten to their children's diets.
    The earlier study, the children did not have a genetic predisposition to celiac disease.
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    SOURCE: Clinical Gastroenterology and Hepatology, October 07, 2015. DOI: http://dx.doi.org/10.1016/j.cgh.2015.09.030

  • Recent Articles

    Jefferson Adams
    Celiac.com 07/19/2018 - Maintaining a gluten-free diet can be an on-going challenge, especially when you factor in all the hidden or obscure gluten that can trip you up. In many cases, foods that are naturally gluten-free end up contain added gluten. Sometimes this can slip by us, and that when the suffering begins. To avoid suffering needlessly, be sure to keep a sharp eye on labels, and beware of added or hidden gluten, even in food labeled gluten-free.  Use Celiac.com's SAFE Gluten-Free Food List and UNSAFE Gluten-free Food List as a guide.
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    Jefferson Adams
    Celiac.com 07/18/2018 - Despite many studies on immune development in children, there still isn’t much good data on how a mother’s diet during pregnancy and infancy influences a child’s immune development.  A team of researchers recently set out to assess whether changes in maternal or infant diet might influence the risk of allergies or autoimmune disease.
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    They are variously associated with the Department of Undiagnosed Celiac Disease More Common in Women and Girls International Health, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America; the Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom; the Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom; the Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; the Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; the Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom; and Stanford University in the USA.
    Team members searched MEDLINE, Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) for observational studies conducted between January 1946 and July 2013, and interventional studies conducted through December 2017, that evaluated the relationship between diet during pregnancy, lactation, or the first year of life, and future risk of allergic or autoimmune disease. 
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    Stay tuned for more on diet during pregnancy and its role in celiac disease.
    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
    Celiac.com 07/17/2018 - What can fat soluble vitamin levels in newly diagnosed children tell us about celiac disease? A team of researchers recently assessed fat soluble vitamin levels in children diagnosed with newly celiac disease to determine whether vitamin levels needed to be assessed routinely in these patients during diagnosis.
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    Vitamin A and vitamin D levels for celiac patients were significantly lower than the control group. Vitamin A and vitamin D deficiencies were significantly more common compared to healthy subjects. Nearly all of the celiac patients showed vitamin D insufficiency, while nearly 62% showed vitamin D deficiency. Nearly 33% of celiac patients showed vitamin A deficiency. 
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    Source:
    BMC Pediatrics

    Jefferson Adams
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    Read more at azcentral.com.

    Jefferson Adams
    Celiac.com 07/14/2018 - If you’re looking for a simple, nutritious and exciting alternative to standard spaghetti and tomato sauce, look no further than this delicious version that blends ripe plum tomatoes, garlic, olive oil, basil, and firm sliced ricotta to deliver a tasty, memorable dish.
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