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Bose D. Introduction to Nutrition and Autoimmune Diseases. ADVANCES IN MEDICAL DIAGNOSIS, TREATMENT, AND CARE 2024:415-431. [DOI: 10.4018/979-8-3693-5528-2.ch015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Celiac disease is an autoimmune hereditary disorder that occurs in genetically predisposed people where the ingestion of gluten leads to damage in their small intestine. When people with celiac disease consume gluten, their body mounts an immune response that attacks the villi of small intestine, which are small finger like projections that promote nutrient absorption. A damaged villi is incapable of absorbing food properly. If left untreated, celiac disease can lead to additional serious health problems. Gluten free diet is the only option to keep the symptoms low. Recently, probiotics have acquired significant attention because of their potential benefits in a wide range of biomedical applications. Thus, administering probiotics as a plausible therapeutic measure for improving the gut health and overall quality of life of patients suffering with this disease is of notable concern. The chapter aims to examine such probiotic applications for patients suffering from celiac disease through comprehensive literature analysis with emphasis on dietary supplements and requirements.
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du Pre MF, Iversen R, Sollid LM. Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies. Gut 2024; 73:844-853. [PMID: 38378252 DOI: 10.1136/gutjnl-2023-331595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 01/30/2024] [Indexed: 02/22/2024]
Abstract
Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure have been dissected. This review presents the current insights demonstrating that the autoantibodies in coeliac disease are intimately integrated in the maladapted immune response to gluten.
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Affiliation(s)
- M Fleur du Pre
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
| | - Rasmus Iversen
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
| | - Ludvig M Sollid
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
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Grizzi F, Hegazi MA. Functional foods and celiac disease prevalent in North America and globally. FUNCTIONAL FOODS AND CHRONIC DISEASE 2024:105-114. [DOI: 10.1016/b978-0-323-91747-6.00006-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Besser HA, Khosla C. Celiac disease: mechanisms and emerging therapeutics. Trends Pharmacol Sci 2023; 44:949-962. [PMID: 37839914 PMCID: PMC10843302 DOI: 10.1016/j.tips.2023.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 09/14/2023] [Accepted: 09/20/2023] [Indexed: 10/17/2023]
Abstract
Celiac disease (CeD) is a widespread, gluten-induced, autoimmune disorder that lacks any medicinal therapy. Towards the goal of developing non-dietary treatments for CeD, research has focused on elucidating its molecular and cellular etiology. A model of pathogenesis has emerged centered on interactions between three molecular families: specific class II MHC proteins on antigen-presenting cells (APCs), deamidated gluten-derived peptides, and T cell receptors (TCRs) on inflammatory CD4+ T cells. Growing evidence suggests that this pathogenic axis can be pharmacologically targeted to protect patients from some of the adverse effects of dietary gluten. Further studies have revealed the existence of additional host and environmental contributors to disease initiation and tissue damage. This review summarizes our current understanding of CeD pathogenesis and how it is being harnessed for therapeutic design and development.
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Affiliation(s)
- Harrison A Besser
- Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Chaitan Khosla
- Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Sarafan ChEM-H (Chemistry, Engineering and Medicine for Human Health), Stanford University, Stanford, CA 94305, USA.
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5
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Knip M. Similarities and dissimilarities between type 1 diabetes and coeliac disease. Acta Paediatr 2023; 112:2030-2031. [PMID: 37574660 DOI: 10.1111/apa.16940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 07/29/2023] [Accepted: 08/04/2023] [Indexed: 08/15/2023]
Affiliation(s)
- Mikael Knip
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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Giuffrè M, Gazzin S, Zoratti C, Llido JP, Lanza G, Tiribelli C, Moretti R. Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation. Int J Mol Sci 2022; 23:15564. [PMID: 36555205 PMCID: PMC9779232 DOI: 10.3390/ijms232415564] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/04/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Celiac disease (CD) is a complex multi-organ disease with a high prevalence of extra-intestinal involvement, including neurological and psychiatric manifestations, such as cerebellar ataxia, peripheral neuropathy, epilepsy, headache, cognitive impairment, and depression. However, the mechanisms behind the neurological involvement in CD remain controversial. Recent evidence shows these can be related to gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and in severe cases, vitamins or nutrients deficiency. Here, we have summarized new evidence related to gut microbiota and the so-called "gut-liver-brain axis" involved in CD-related neurological manifestations. Additionally, there has yet to be an agreement on whether serological or neurophysiological findings can effectively early diagnose and properly monitor CD-associated neurological involvement; notably, most of them can revert to normal with a rigorous gluten-free diet. Moving from a molecular level to a symptom-based approach, clinical, serological, and neurophysiology data might help to disentangle the many-faceted interactions between the gut and brain in CD. Eventually, the identification of multimodal biomarkers might help diagnose, monitor, and improve the quality of life of patients with "neuroCD".
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Affiliation(s)
- Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - Silvia Gazzin
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
| | - Caterina Zoratti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - John Paul Llido
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
- Department of Life Sciences, University of Trieste, 34128 Trieste, Italy
- Philippine Council for Healthcare Research and Development, Department of Science and Technology, Bicutan Taguig City 1631, Philippines
| | - Giuseppe Lanza
- Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy
- Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, 94018 Troina, Italy
| | - Claudio Tiribelli
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
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Anderson RP. Review article: Diagnosis of coeliac disease: a perspective on current and future approaches. Aliment Pharmacol Ther 2022; 56 Suppl 1:S18-S37. [PMID: 35815826 DOI: 10.1111/apt.16840] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/08/2022] [Accepted: 02/08/2022] [Indexed: 12/09/2022]
Abstract
Diagnostics will play a central role in addressing the ongoing dramatic rise in global prevalence of coeliac disease, and in deploying new non-dietary therapeutics. Clearer understanding of the immunopathogenesis of coeliac disease and the utility of serology has led to partial acceptance of non-biopsy diagnosis in selected cases. Non-biopsy diagnosis may expand further because research methods for measuring gluten-specific CD4+ T cells and the acute recall response to gluten ingestion in patients is now relatively straightforward. This perspective on diagnosis in the context of the immunopathogenesis of coeliac disease sets out to highlight current consensus, limitations of current practices, gluten food challenge for diagnosis and the potential for diagnostics that measure the underlying cause for coeliac disease, gluten-specific immunity.
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Ciacchi L, Reid HH, Rossjohn J. Structural bases of T cell antigen receptor recognition in celiac disease. Curr Opin Struct Biol 2022; 74:102349. [PMID: 35272251 DOI: 10.1016/j.sbi.2022.102349] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 01/15/2022] [Accepted: 01/30/2022] [Indexed: 12/16/2022]
Abstract
Celiac disease (CeD) is a human leukocyte antigen (HLA)-linked autoimmune-like disorder that is triggered by the ingestion of gluten or related storage proteins. The majority of CeD patients are HLA-DQ2.5+, with the remainder being either HLA-DQ8+ or HLA-DQ2.2+. Structural studies have shown how deamidation of gluten epitopes engenders binding to HLA-DQ2.5/8, which then triggers an aberrant CD4+ T cell response. HLA tetramer studies, combined with structural investigations, have demonstrated that repeated patterns of TCR usage underpins the immune response to some HLADQ2.5/8 restricted gluten epitopes, with distinct TCR motifs representing common landing pads atop the HLA-gluten complexes. Structural studies have provided insight into TCR specificity and cross-reactivity towards gluten epitopes, as well as cross-reactivity to bacterial homologues of gluten epitopes, suggesting that environmental factors may directly play a role in CeD pathogenesis. Collectively, structural immunology-based studies in the CeD axis may lead to new therapeutics/diagnostics to treat CeD, and also serve as an exemplar for other T cell mediated autoimmune diseases.
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Affiliation(s)
- Laura Ciacchi
- Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia
| | - Hugh H Reid
- Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia
| | - Jamie Rossjohn
- Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, United Kingdom.
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de Sousa Franckilin LR, Dos Santos ACPM, Freitas FEDA, Vieira IG, de Freitas Jorge CE, Neri DG, de Abreu MVC, Fonseca JK, Loffi RG, Foureaux G. Gluten: do only celiac patients benefit from its removal from the diet? FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2021.2024566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
| | | | | | | | | | | | | | | | - Renato Guimarães Loffi
- Departamento de Ciência, Tecnologia e Inovação, Treini Biotecnologia Ltda, Belo Horizonte, Brazil
| | - Giselle Foureaux
- Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Departamento de Nutrição, Angiogold: Medicina Integrativa, Belo Horizonte, Brazil
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Anderson RP. Emergence of an adaptive immune paradigm to explain celiac disease: a perspective on new evidence and implications for future interventions and diagnosis. Expert Rev Clin Immunol 2021; 18:75-91. [PMID: 34767744 DOI: 10.1080/1744666x.2021.2006636] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Recent patient studies have shown that gluten-free diet is less effective in treating celiac disease than previously believed, and additionally patients remain vulnerable to gluten-induced acute symptoms and systemic cytokine release. Safe and effective pharmacological adjuncts to gluten-free diet are in preclinical and clinical development. Clear understanding of the pathogenesis of celiac disease is critical for drug target identification, establishing efficacy endpoints and to develop non-invasive biomarkers suitable to monitor and potentially diagnose celiac disease. AREAS COVERED The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an "adaptive immune paradigm" are reviewed. Alternative hypotheses of gluten toxicity are discussed and contrasted. In the context of recent patient studies, implications of the adaptive immune paradigm for future strategies to prevent, diagnose, and treat celiac disease are outlined. EXPERT OPINION Effective therapeutics for celiac disease are likely to be approved and necessitate a variety of new clinical instruments and tests to stratify patient need, monitor remission, and confirm diagnosis in uncertain cases. Sensitive assessments of CD4+ T cells specific for deamidated gluten are likely to play a central role in clinical management, and to facilitate research and pharmaceutical development.
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Onyimba F, Crowe SE, Johnson S, Leung J. Food Allergies and Intolerances: A Clinical Approach to the Diagnosis and Management of Adverse Reactions to Food. Clin Gastroenterol Hepatol 2021; 19:2230-2240.e1. [PMID: 33493695 DOI: 10.1016/j.cgh.2021.01.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/18/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
Food allergy is an aberrant immunological response to food antigen, which can result in potentially life-threatening reactions. It is often challenging to differentiate food allergy from other adverse reactions to food because their presentations can be indistinguishable. The purpose of this article is to give an overview of the classification, evaluation, and management of adverse food reactions, key differentiating features of food allergy, roles and limitations of various food allergy testing, and promising areas of emerging research. Case studies are used to highlight some of the clinical pearls in diagnosing and managing food-related diseases.
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Affiliation(s)
- Frances Onyimba
- University of Maryland School of Medicine, Baltimore, Maryland.
| | - Sheila E Crowe
- University of California San Diego, La Jolla, California
| | | | - John Leung
- Boston Food Allergy Center, Boston, Massachusetts; Tufts Medical Center, Boston, Massachusetts.
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Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols. Int J Mol Sci 2021; 22:ijms22020595. [PMID: 33435615 PMCID: PMC7826989 DOI: 10.3390/ijms22020595] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/04/2021] [Accepted: 01/05/2021] [Indexed: 12/13/2022] Open
Abstract
Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.
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De Vincenzi M, Dessì MR, Luchetti R, Pogna N, Redaelli R, Galterio G. Toxicity of Bread Wheat Lines Lacking Prolamins Encoded by theGli-B1/Gli-B5/Glu-B3andGli-D1/Glu-D3Loci in Coeliac Disease as Determined by their Agglutinating Activity. Altern Lab Anim 2020. [DOI: 10.1177/026119299602400107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Peptic-tryptic (PT) digests of alcohol-soluble proteins from the flour of three mutant lines of bread wheat, lacking γ-gliadins, γ-gliadins and low molecular-weight glutenin subunits encoded by the Gli-B1/Gli-B5/Glu-B3 loci (line S. Pastore 4A), the Gli-D1/Glu-D3 loci (line Alpe 1I-) or both groups of loci (line DM 22166), were compared with those of the normal cultivars S. Pastore and Alpe 1 I for their agglutinating activities on human myelogenous leukemia K562(S) cells, agglutination being strongly associated with toxicity for the coeliac intestine. All of the genotypes tested contained A-type α-gliadins, which constituted about 19% of the gliadins in the S. Pastore and Alpe 1I cultivars, 24.5% in the S. Pastore 4A and Alpe 1I null lines, and 34.8% in the double mutant line, DM 22166, as determined by densitometric scanning of their acid polyacrylamide gel electrophoresis patterns. The minimal concentrations of PT digest required to agglutinate 100% of K562(S) cells were 73mg/l and 96mg/l, in the S. Pastore and Alpe 1I cultivars, respectively, compared with 146mg/l, 138mg/l and 200mg/l in the “null” lines, S. Pastore 4A, Alpe 1 I-and DM 22166, respectively. The results indicated that proteins other than α-gliadins are involved in the gluten-sensitive enteropathy.
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Affiliation(s)
- Massimo De Vincenzi
- Laboratorio di Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
| | - Maria R. Dessì
- Laboratorio di Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
| | - Roberto Luchetti
- Laboratorio di Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
| | - Norberto Pogna
- Istituto Sperimentale Cerealicoltura, Via Cassia 176, 00191 Rome, Italy
| | - Rita Redaelli
- Istituto Sperimentale Cerealicoltura, Via Mulino 3, 20079 S. Angela Lodigiano, Italy
| | - Giovanni Galterio
- Istituto Sperimentale Cerealicoltura, Via Cassia 176, 00191 Rome, Italy
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15
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Giovannini C, Luchetti R, De Vincenzi M. The activities of peptides “31–43”, “44–55” and “56–68” of A-gliadin onIn VitroCultures of CaCo-2 Cells. Altern Lab Anim 2020. [DOI: 10.1177/026119299702500406] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In previous studies, various A-gliadin peptides with known amino acid sequences have been tested for their damaging effects on in vitro cultured atrophic coeliac mucosa. The largest common sequences among the in vitro toxic peptides were (gln)3- pro and pro-ser-(gln)2. Three of these active A-gliadin fragments were synthesised and characterised, namely, the peptides corresponding to the amino acid sequences “31–43” and “44–55”, which contain the sequences (gln)3-rpro and pro-ser-(gln)2, respectively, and the “56–68” fragment lacking both active amino acid sequences. While the “56–68” A-gliadin peptide was completely inactive in CaCo-2 cells, the other two peptides were cytotoxic toward these cells to different extents. Our results confirm that CaCo-2 cells are a suitable model for the identification of toxic peptides responsible for coeliac pathogenesis.
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Affiliation(s)
- Claudio Giovannini
- Laboratorio i Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 209, 00161 Rome, Italy
| | - Roberto Luchetti
- Laboratorio i Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 209, 00161 Rome, Italy
| | - Massimo De Vincenzi
- Laboratorio i Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 209, 00161 Rome, Italy
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Hardy MY, Russell AK, Pizzey C, Jones CM, Watson KA, La Gruta NL, Cameron DJ, Tye-Din JA. Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease. Gut 2020; 69:830-840. [PMID: 31462555 DOI: 10.1136/gutjnl-2019-319093] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/23/2019] [Accepted: 08/15/2019] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD. DESIGN 42 children with human leucocyte antigen (HLA)-DQ2.5+ (aged 3-17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD. RESULTS 90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults. CONCLUSIONS Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.
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Affiliation(s)
- Melinda Y Hardy
- Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Amy K Russell
- Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Catherine Pizzey
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Claerwen M Jones
- Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
| | - Katherine A Watson
- Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Nicole L La Gruta
- Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
| | - Donald J Cameron
- Department of Gastroenterology and Clinical Nutrition, The Royal Children's Hospital, Parkville, Victoria, Australia
| | - Jason A Tye-Din
- Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia .,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.,Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Parkville, Victoria, Australia
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Villanueva M, Oyarzún A, Leyton B, González M, Navarro E, Canales P, Ossa C, Muñoz MP, Bascuñán KA, Araya M. Changes in Age at Diagnosis and Nutritional Course of Celiac Disease in the Last Two Decades. Nutrients 2020; 12:nu12010156. [PMID: 31935859 PMCID: PMC7019995 DOI: 10.3390/nu12010156] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 12/31/2019] [Accepted: 01/02/2020] [Indexed: 12/13/2022] Open
Abstract
The frequency of celiac disease (CD) has increased along time, with relevant changes reported in geographical variations, clinical presentation and nutritional repercussions. In recent years, some celiac patients are presenting overweight/obesity, but it is unclear how frequent this is and to what extent undernutrition remains a concern. This is relevant because CD tends to be overlooked in overweight patients. With this in mind, we assessed age at diagnosis, clinical characteristics and nutritional status of 155 celiac patients diagnosed between 1994–2017 in four pediatric hospitals in Santiago, Chile. Since 2003, the number of patients diagnosed has increased (p < 0.0033), coinciding with antitransglutaminase and antiendomysial antibodies becoming available to public health systems. In 2000, 4.5% of patients were asymptomatic at diagnosis, suggesting that active search is not routinely applied. Gastrointestinal symptoms plus failure to thrive were significantly more frequent under 2 years (p = 0.0001). Nutritional status has improved at diagnosis and during follow up, but undernutrition remains more frequent in children <2 and <5 years (p < 0.002 and p < 0.0036, respectively). Overweight at diagnosis was reported in 2002 and obesity in 2010. After initiating treatment, since 2010, patients changing from undernourishment to overweight has sometimes been observed after only 6 months on a gluten-free diet.
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Affiliation(s)
- Mónica Villanueva
- Fellow, Pediatric Gastroenterology and Nutrition Program, Faculty of Medicine, University of Chile, Santiago, Chile, Clínica Alemana de Santiago, Chile;
| | - Amaya Oyarzún
- Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; (A.O.); (B.L.); (K.A.B.)
| | - Bárbara Leyton
- Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; (A.O.); (B.L.); (K.A.B.)
| | | | | | - Paulina Canales
- Hospital Exequiel González Cortés, Santiago, Chile; (E.N.); (P.C.)
| | - Cristobal Ossa
- Hospital Luis Calvo Mackenna, Santiago, Chile; (C.O.); (M.P.M.)
| | - María Paz Muñoz
- Hospital Luis Calvo Mackenna, Santiago, Chile; (C.O.); (M.P.M.)
| | - Karla A. Bascuñán
- Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; (A.O.); (B.L.); (K.A.B.)
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Magdalena Araya
- Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; (A.O.); (B.L.); (K.A.B.)
- Correspondence:
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18
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Dahal-Koirala S, Neumann RS, Jahnsen J, Lundin KEA, Sollid LM. On the immune response to barley in celiac disease: Biased and public T-cell receptor usage to a barley unique and immunodominant gluten epitope. Eur J Immunol 2019; 50:256-269. [PMID: 31628754 DOI: 10.1002/eji.201948253] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 09/03/2019] [Accepted: 10/16/2019] [Indexed: 01/17/2023]
Abstract
Celiac disease (CeD) is driven by CD4+ T-cell responses to dietary gluten proteins of wheat, barley, and rye when deamidated gluten epitopes are presented by certain disease-associated HLA-DQ allotypes. About 90% of the CeD patients express HLA-DQ2.5. In such patients, five gluten epitopes dominate the anti-gluten T-cell response; two epitopes unique to wheat, two epitopes present in wheat, barley, and rye and one epitope unique to barley. Despite presence of barley in commonly consumed food and beverages and hence being a prominent source of gluten, knowledge about T-cell responses elicited by barley in CeD is scarce. Therefore, in this study, we explored T-cell response toward the barley unique epitope DQ2.5-hor-3 (PIPEQPQPY) by undertaking HLA-DQ:gluten peptide tetramer staining, single-cell T-cell receptor (TCR) αβ sequencing, T-cell cloning, and T-cell proliferation studies. We demonstrate that majority of the CeD patients generate T-cell response to DQ2.5-hor-3, and this response is characterized by clonal expansion, preferential TCR V-gene usage and public TCR features thus echoing findings previously made for wheat gluten epitopes. The knowledge that biased and public TCRs underpin the T-cell response to all the immunodominant gluten epitopes in CeD suggests that such T cells are promising diagnostic and therapeutic targets.
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Affiliation(s)
- Shiva Dahal-Koirala
- K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, Oslo, Norway.,Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ralf S Neumann
- K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, Oslo, Norway.,Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Knut E A Lundin
- K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Ludvig M Sollid
- K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, Oslo, Norway.,Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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19
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Tanner G, Juhász A, Florides CG, Nye-Wood M, Békés F, Colgrave ML, Russell AK, Hardy MY, Tye-Din JA. Preparation and Characterization of Avenin-Enriched Oat Protein by Chill Precipitation for Feeding Trials in Celiac Disease. Front Nutr 2019; 6:162. [PMID: 31681788 PMCID: PMC6803533 DOI: 10.3389/fnut.2019.00162] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 09/26/2019] [Indexed: 12/15/2022] Open
Abstract
The safety of oats for people with celiac disease remains unresolved. While oats have attractive nutritional properties that can improve the quality and palatability of the restrictive, low fiber gluten-free diet, rigorous feeding studies to address their safety in celiac disease are needed. Assessing the oat prolamin proteins (avenins) in isolation and controlling for gluten contamination and other oat components such as fiber that can cause non-specific effects and symptoms is crucial. Further, the avenin should contain all reported immunogenic T cell epitopes, and be deliverable at a dose that enables biological responses to be correlated with clinical effects. To date, isolation of a purified food-grade avenin in sufficient quantities for feeding studies has not been feasible. Here, we report a new gluten isolation technique that enabled 2 kg of avenin to be extracted from 400 kg of wheat-free oats under rigorous gluten-free and food grade conditions. The extract consisted of 85% protein of which 96% of the protein was avenin. The concentration of starch (1.8% dry weight), β-glucan (0.2% dry weight), and free sugars (1.8% dry weight) were all low in the final avenin preparation. Other sugars including oligosaccharides, small fructans, and other complex sugars were also low at 2.8% dry weight. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the proteins in these preparations showed they consisted only of oat proteins and were uncontaminated by gluten containing cereals including wheat, barley or rye. Proteomic analysis of the avenin enriched samples detected more avenin subtypes and fewer other proteins compared to samples obtained using other extraction procedures. The identified proteins represented five main groups, four containing known immune-stimulatory avenin peptides. All five groups were identified in the 50% (v/v) ethanol extract however the group harboring the epitope DQ2.5-ave-1b was less represented. The avenin-enriched protein fractions were quantitatively collected by reversed phase HPLC and analyzed by MALDI-TOF mass spectrometry. Three reverse phase HPLC peaks, representing ~40% of the protein content, were enriched in proteins containing DQ2.5-ave-1a epitope. The resultant high quality avenin will facilitate controlled and definitive feeding studies to establish the safety of oat consumption by people with celiac disease.
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Affiliation(s)
- Greg Tanner
- School of Biosciences, University of Melbourne, Melbourne, VIC, Australia
| | - Angéla Juhász
- School of Science, Edith Cowan University, Joondalup, WA, Australia
| | | | | | | | | | - Amy K. Russell
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
| | - Melinda Y. Hardy
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
| | - Jason A. Tye-Din
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia
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20
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Celiac Disease and the Microbiome. Nutrients 2019; 11:nu11102403. [PMID: 31597349 PMCID: PMC6835875 DOI: 10.3390/nu11102403] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/26/2019] [Accepted: 09/27/2019] [Indexed: 02/07/2023] Open
Abstract
Growing evidence supports the hypothesis that changes in both the composition and function of the intestinal microbiome are associated with a number of chronic inflammatory diseases including celiac disease (CD). One of the major advances in the field of microbiome studies over the last few decades has been the development of culture-independent approaches to identify and quantify the components of the human microbiota. The study of nucleic acids DNA and RNA found in feces or other biological samples bypasses the need for tissue cultures and also allows the characterization of non-cultivable microbes. Current evidence on the composition of the intestinal microbiome and its role as a causative trigger for CD is highly heterogeneous and sometimes contradictory. This review is aimed at summarizing both pre-clinical (basic science data) and clinical (cross-sectional and prospective studies) evidence addressing the relationship between the intestinal microbiome and CD.
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21
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Spector Cohen I, Day AS, Shaoul R. To Be Oats or Not to Be? An Update on the Ongoing Debate on Oats for Patients With Celiac Disease. Front Pediatr 2019; 7:384. [PMID: 31616650 PMCID: PMC6775206 DOI: 10.3389/fped.2019.00384] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022] Open
Abstract
To date, the only known effective treatment for celiac disease (CD) is a strict gluten-free diet (GFD) for life. Patients with CD often find it difficult to adhere to strict GFD. Oats, compared with wheat, barley, and rye, contain less amounts of prolamins. Inclusion of oats in a GFD might be valuable due to their nutritional and health benefits and increase of food variety. Therefore, they may potentially improve feeding diversity for these children and improve taste and satiety. We reviewed the literature to evaluate the safety of oats in CD patients. We have searched PUBMED, societal guidelines and national health authorities' recommendations. The following aspects were reviewed: gastrointestinal symptoms, malabsorption, serology including specific avenin antibodies, mucosal changes, avenin toxicity, immunogenicity of oats, and quality of life. We also referred to wheat contamination of oat products, the safe amount of oats for CD patients and the type of oats recommended. Data support that pure oats are well-tolerated by most CD patients, at moderate amounts (20-25 g/day dry rolled oats for children; 50-70 g/day for adults). Nevertheless, since the potential for sensitivity/toxicity exists, oats should be added with caution to a GFD, only after all CD symptoms including weight loss and growth disturbances have resolved, after at least 6 months of conventional GFD and probably also after normalization of serology. The need for pre exposure biopsy is unclear and should be considered on an individual basis.
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Affiliation(s)
- Inna Spector Cohen
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
| | - Andrew S. Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Ron Shaoul
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
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22
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Jouanin A, Schaart JG, Boyd LA, Cockram J, Leigh FJ, Bates R, Wallington EJ, Visser RGF, Smulders MJM. Outlook for coeliac disease patients: towards bread wheat with hypoimmunogenic gluten by gene editing of α- and γ-gliadin gene families. BMC PLANT BIOLOGY 2019; 19:333. [PMID: 31370789 PMCID: PMC6670228 DOI: 10.1186/s12870-019-1889-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 06/17/2019] [Indexed: 05/20/2023]
Abstract
BACKGROUND Wheat grains contain gluten proteins, which harbour immunogenic epitopes that trigger Coeliac disease in 1-2% of the human population. Wheat varieties or accessions containing only safe gluten have not been identified and conventional breeding alone struggles to achieve such a goal, as the epitopes occur in gluten proteins encoded by five multigene families, these genes are partly located in tandem arrays, and bread wheat is allohexaploid. Gluten immunogenicity can be reduced by modification or deletion of epitopes. Mutagenesis technologies, including CRISPR/Cas9, provide a route to obtain bread wheat containing gluten proteins with fewer immunogenic epitopes. RESULTS In this study, we analysed the genetic diversity of over 600 α- and γ-gliadin gene sequences to design six sgRNA sequences on relatively conserved domains that we identified near coeliac disease epitopes. They were combined in four CRISPR/Cas9 constructs to target the α- or γ-gliadins, or both simultaneously, in the hexaploid bread wheat cultivar Fielder. We compared the results with those obtained with random mutagenesis in cultivar Paragon by γ-irradiation. For this, Acid-PAGE was used to identify T1 grains with altered gliadin protein profiles compared to the wild-type endosperm. We first optimised the interpretation of Acid-PAGE gels using Chinese Spring deletion lines. We then analysed the changes generated in 360 Paragon γ-irradiated lines and in 117 Fielder CRISPR/Cas9 lines. Similar gliadin profile alterations, with missing protein bands, could be observed in grains produced by both methods. CONCLUSIONS The results demonstrate the feasibility and efficacy of using CRISPR/Cas9 to simultaneously edit multiple genes in the large α- and γ-gliadin gene families in polyploid bread wheat. Additional methods, generating genomics and proteomics data, will be necessary to determine the exact nature of the mutations generated with both methods.
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Affiliation(s)
- Aurélie Jouanin
- Wageningen University and Research, Plant Breeding, Wageningen, The Netherlands
- The John Bingham Laboratory, NIAB, Huntingdon Road, Cambridge, UK
| | - Jan G. Schaart
- Wageningen University and Research, Plant Breeding, Wageningen, The Netherlands
| | - Lesley A. Boyd
- The John Bingham Laboratory, NIAB, Huntingdon Road, Cambridge, UK
| | - James Cockram
- The John Bingham Laboratory, NIAB, Huntingdon Road, Cambridge, UK
| | - Fiona J. Leigh
- The John Bingham Laboratory, NIAB, Huntingdon Road, Cambridge, UK
| | - Ruth Bates
- The John Bingham Laboratory, NIAB, Huntingdon Road, Cambridge, UK
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23
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Pei J, Wei S, Pei Y, Wu H, Wang D. Role of Dietary Gluten in Development of Celiac Disease and Type I Diabetes: Management Beyond Gluten-Free Diet. Curr Med Chem 2019; 27:3555-3576. [PMID: 30963964 DOI: 10.2174/0929867326666190409120716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 03/25/2019] [Accepted: 04/03/2019] [Indexed: 11/22/2022]
Abstract
Gluten triggers Celiac Disease (CD) and type I diabetes in genetically predisposed population of human leukocyte antigen DQ2/DQ8+ and associates with disorders such as schizophrenia and autism. Application of a strict gluten-free diet is the only well-established treatment for patients with CD, whereas the treatment for patients with celiac type I diabetes may be depend on the timing and frequency of the diet. The application of a gluten-free diet in patients with CD may contribute to the development of metabolic syndrome and nonalcoholic fatty liver disease and may also lead to a high glycemic index, low fiber diet and micronutrient deficiencies. The alteration of copper bioavailability (deficient, excess or aberrant coordination) may contribute to the onset and progress of related pathologies. Therefore, nutrient intake of patients on a gluten-free diet should be the focus of future researches. Other gluten-based therapies have been rising with interest such as enzymatic pretreatment of gluten, oral enzyme supplements to digest dietary gluten, gluten removal by breeding wheat varieties with reduced or deleted gluten toxicity, the development of polymeric binders to suppress gluten induced pathology.
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Affiliation(s)
- Jinli Pei
- Hainan Province Key Laboratory for Sustainable Utilization of Tropical Bioresources, Hainan University, Hainan, 570228, China.,Laboratory of Biotechnology and Molecular Pharmacology, School of Life and Pharmaceutical Sciences, Hainan University, Hainan 570228, China
| | - Shuangshuang Wei
- Hainan Province Key Laboratory for Sustainable Utilization of Tropical Bioresources, Hainan University, Hainan, 570228, China.,Laboratory of Biotechnology and Molecular Pharmacology, School of Life and Pharmaceutical Sciences, Hainan University, Hainan 570228, China
| | - Yechun Pei
- Hainan Province Key Laboratory for Sustainable Utilization of Tropical Bioresources, Hainan University, Hainan, 570228, China.,Laboratory of Biotechnology and Molecular Pharmacology, School of Life and Pharmaceutical Sciences, Hainan University, Hainan 570228, China
| | - Hao Wu
- Hainan Province Key Laboratory for Sustainable Utilization of Tropical Bioresources, Hainan University, Hainan, 570228, China.,Laboratory of Biotechnology and Molecular Pharmacology, School of Life and Pharmaceutical Sciences, Hainan University, Hainan 570228, China
| | - Dayong Wang
- Hainan Province Key Laboratory for Sustainable Utilization of Tropical Bioresources, Hainan University, Hainan, 570228, China.,Laboratory of Biotechnology and Molecular Pharmacology, School of Life and Pharmaceutical Sciences, Hainan University, Hainan 570228, China
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24
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Lagana SM, Bhagat G. Biopsy Diagnosis of Celiac Disease: The Pathologist's Perspective in Light of Recent Advances. Gastroenterol Clin North Am 2019; 48:39-51. [PMID: 30711210 DOI: 10.1016/j.gtc.2018.09.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
Celiac disease is a common immune-mediated disorder that occurs in individuals with permissive genetics (HLA-DQ2/DQ8 genotype) following exposure to certain wheat proteins. The histopathologic manifestations of small intestinal mucosal injury (villus atrophy, crypt hyperplasia, and intraepithelial lymphocytosis) are well recognized. However, these findings are not specific for celiac disease, because they are observed in other small intestinal disorders. These mimics include common and rare entities, the list of which continues to grow. This article discusses the histopathology and differential diagnosis of celiac disease and provides the pathologist's perspective on biopsy adequacy, evaluation, and reporting in light of current knowledge.
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Affiliation(s)
- Stephen M Lagana
- Columbia University, New York Presbyterian Hospital, 622 West 168th Street, VC14-209, New York, NY 10032, USA.
| | - Govind Bhagat
- Columbia University, New York Presbyterian Hospital, 622 West 168th Street, VC14-228, New York, NY 10032, USA
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25
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Tighe MP, Beattie RM. Searching for the missing link in coeliac disease. BMJ 2019; 364:l696. [PMID: 30760440 DOI: 10.1136/bmj.l696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- M P Tighe
- Department of Paediatrics, Poole Hospital NHS Foundation Trust, Poole, UK
| | - R Mark Beattie
- Child Health, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton S016 6YD, UK
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26
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An unusual Chinese case of celiac disease presenting as hypocalcemia and low bone density. Arch Osteoporos 2019; 14:7. [PMID: 30631967 DOI: 10.1007/s11657-019-0557-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 01/03/2019] [Indexed: 02/03/2023]
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27
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Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): Captivating Witness Reports of a Success Story. J Pediatr Gastroenterol Nutr 2018; 66 Suppl 1:S154-S171. [PMID: 29596189 DOI: 10.1097/mpg.0000000000001919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Since the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan-European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.
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28
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Taylor JP, Jacob F, Arendt EK. Fundamental Study on the Impact of Transglutaminase on Hordein Levels in Beer. JOURNAL OF THE AMERICAN SOCIETY OF BREWING CHEMISTS 2018. [DOI: 10.1094/asbcj-2015-0527-01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
| | - Fritz Jacob
- Research Center Weihenstephan for Brewing and Food Quality, Technische Universität München, Germany
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Abstract
OBJECTIVES Some evidence suggests that prevalence of celiac disease in the general population is increasing over time. Because the prognosis of celiac disease was a dismal one before discovering the role of gluten, our aim was to investigate a possible relationship between children under-5 mortality rates and prevalence rates of celiac disease. METHODS Thanks to a literature review, we found 27 studies performed in 17 different countries describing the prevalence of celiac disease in schoolchildren; between 1995 and 2011, 4 studies were performed in Italy. A meta-analysis of prevalence rates was performed. Prevalence was compared between specific country under-5 mortality groups, publication year, and age. RESULTS In the last decades, under-5 mortality rates have been decreasing all over the world. This reduction is paralleled by an increase of the prevalence of celiac disease. The Spearman correlation coefficient was -63%, 95% confidence interval -82% to -33% (P < 0.001). So, the higher the mortality rate, the lower the prevalence of CD. This finding is confirmed by the meta-analysis of the 4 studies conducted in Italy over time. CONCLUSIONS The under-5 mortality rate seems to influence the prevalence of celiac disease in the general population. In the near future, the number of patients with celiac disease will increase, thanks to the better environmental conditions that nowadays allow a better survival of children with celiac disease.
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30
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Oats in healthy gluten-free and regular diets: A perspective. Food Res Int 2017; 110:3-10. [PMID: 30029703 DOI: 10.1016/j.foodres.2017.11.031] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 11/11/2017] [Accepted: 11/19/2017] [Indexed: 12/11/2022]
Abstract
During the 20th century, the economic position of oats (Avena sativa L.) decreased strongly in favour of higher yielding crops including winter wheat and maize. Presently, oat represents only ~1.3% of the total world grain production, and its production system is fragmented. Nonetheless, current interest is growing because of recent knowledge on its potential benefits in food, feed and agriculture. This perspective will serve as a further impetus, with special focus on the recently valued advantages of oats in human food and health. Five approved European Food Safety Authority (EFSA) health claims apply to oats. Four relate to the oat-specific soluble fibres, the beta-glucans, and concern the maintenance and reduction of blood cholesterol, better blood glucose balance and increased faecal bulk. The fifth claim concerns the high content of unsaturated fatty acids, especially present in the endosperm, which reduces the risks of heart and vascular diseases. Furthermore, oat starch has a low glycemic index, which is favourable for weight control. Oat-specific polyphenols and avenanthramides have antioxidant and anti-inflammatory properties. Thus, oats can contribute significantly to the presently recommended whole-grain diet. Next to globulins, oats contain a small fraction of prolamin storage proteins, called 'avenins', but at a much lower quantity than gluten proteins in wheat, barley and rye. Oat avenins do not contain any of the known coeliac disease epitopes from gluten of wheat, barley and rye. Long-term food studies confirm the safety of oats for coeliac disease patients and the positive health effects of oat products in a gluten-free diet. These effects are general and independent of oat varieties. In the EU (since 2009), the USA (since 2013) and Canada (since 2015) oat products may be sold as gluten-free provided that any gluten contamination level is below 20ppm. Oats are, however, generally not gluten-free when produced in a conventional production chain, because of regular contamination with wheat, barley or rye. Therefore, establishing a separate gluten-free oat production chain requires controlling all steps in the chain; the strict conditions will be discussed. Genomic tools, including a single nucleotide polymorphism (SNP) marker array and a dense genetic map, have recently been developed and will support marker-assisted breeding. In 2015, the Oat Global initiative emerged enabling a world-wide cooperation starting with a data sharing facility on genotypic, metabolic and phenotypic characteristics. Further, the EU project TRAFOON (Traditional Food Networks) facilitated the transfer of knowledge to small- and medium-sized enterprises (SMEs) to stimulate innovations in oat production, processing, products and marketing, among others with regard to gluten-free. Finally, with focus on counteracting market fragmentation of the global oat market and production chains, interactive innovation strategies between customers (consumers) and companies through co-creation are discussed.
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31
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Abstract
Objective and Conclusion: Uncertainty still exists about the use of oats and wheat starch as part of a gluten-free diet in patients with celiac disease (CD). This review should help to clarify the issues at hand. Whereas uncontaminated (from gluten/gliadin) oats and oats from cultivars not containing celiac-activating sequences of proline and glutamine can be used without risk of intestinal damage, wheat starch should not be used, unless it is free of gluten-that is, deglutinized-because even small amounts of gluten over time are able to induce small intestinal mucosal damage.
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Affiliation(s)
- J Rainer Poley
- a Eastern Virginia Medical School , Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics EVMS, and Childrens' Hospital of the King's Daughters , Norfolk , Virginia, (ret).,b Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Brody School of Medicine , East Carolina University , Greenville , North Carolina (ret)
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32
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Amil Dias J. Celiac Disease: What Do We Know in 2017? GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2017; 24:275-278. [PMID: 29255768 PMCID: PMC5731182 DOI: 10.1159/000479881] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 07/31/2017] [Indexed: 12/20/2022]
Abstract
Celiac disease is one of the most prevalent digestive conditions. Diagnosis requires that strict criteria are used so that a life-long gluten-free diet may be correctly prescribed. Although genetic susceptibility has been known for a long time, there have been elusive environmental factors that lead to the occurrence of clinical disease. Many studies have addressed the identification of environmental modifiers, and different lines of research have been tried with variable success and even contradictory results. Infections and age of gluten introduction into the diet in the first few months of life have been evaluated, but a firm relationship could not be established. A recent paper addresses a fascinating hypothesis that could explain how some infectious agents might modulate the immune system and modify response to dietary antigens. Subsequently, animal models with genetic susceptibility were tested, and, indeed, there was abnormal response to gluten. These observations still do not provide final answers about the pathophysiology of celiac disease but certainly lead to progress in the knowledge of gluten sensitization and the role of some environmental factors.
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Affiliation(s)
- Jorge Amil Dias
- Pediatra e Gastrenterologista Pediátrico, Unidade de Gastrenterologia Pediátrica, Centro Hospitalar S. João, Porto, Portugal
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33
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Abstract
OBJECTIVES Growing evidence supports the view that the diagnosis of coeliac disease (CD) can be made by serological tests alone, although this approach is still not widely accepted. We previously showed in retrospective and prospective studies that in adults an IgA-tissue transglutaminase antibody cut-off can be defined above which the positive predictive value for CD is 100%. Following a change in the analytical method for measuring the antibody, our objectives were to re-examine this finding in a larger series of adults to ascertain whether a diagnosis of CD can be reliably made in a proportion of patients without the need for small bowel biopsy and to re-evaluate the diagnostic guidelines used in our centre. PATIENTS AND METHODS A retrospective analysis was done in an unselected series of 270 adult patients who had small bowel biopsies and serum IgA-tissue transglutaminase antibody levels measured from 2009 to 2014. RESULTS At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8×upper limit of normal+2SDs) the positive predictive value for CD in this cohort was 100%; 40% of cases were above this cut-off. CONCLUSION We have verified that a diagnosis of CD can be reliably made in a high proportion of adults based on serology alone using the IgA-tissue transglutaminase antibody method specified. These results add to the body of evidence that small bowel biopsy should no longer be considered mandatory for the diagnosis of CD. On the basis of these results the diagnostic guidelines in our centre have been modified.
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Evolutionary Developments in Interpreting the Gluten-Induced Mucosal Celiac Lesion: An Archimedian Heuristic. Nutrients 2017; 9:nu9030213. [PMID: 28264483 PMCID: PMC5372876 DOI: 10.3390/nu9030213] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 02/22/2017] [Indexed: 02/07/2023] Open
Abstract
The evolving history of the small intestinal biopsy and its interpretation—and misinterpretations—are described in this paper. Certain interpretative errors in the technical approaches to histological assessment are highlighted—even though we may never be rid of them. For example, mucosal “flattening” does not reduce individual villi to their cores, as still seems to be widely believed. Neither is the mucosa undergoing an atrophic process—since it can recover structurally. Rather, the intestinal mucosa manifests a vast hypertrophic response resulting in the formation of large plateaus formed from partially reduced villi and their amalgamation with the now increased height and width of the inter-villous ridges: this is associated with considerable increases in crypt volumes. Sections through mosaic plateaus gives an erroneous impression of the presence of stunted, flat-topped villi which continues to encourage both the continued use of irrelevant “atrophy” terminologies and a marked failure to perceive what random sections through mosaic plateaus actually look like. While reviewing the extensive 40+ year literature on mucosal analysis, we extracted data on intraepithelial lymphocytes (IEL) counts from 607 biopsies, and applied receiver-operating characteristic (ROC)-curve analysis. From that perspective, it appears that counting IEL/100 enterocyte nuclei in routine haematoxylin and eosin (H&E) sections provides the most useful discriminator of celiac mucosae at histological level, with an effective cut-off of 27 IEL, and offering a very high sensitivity with few false negatives. ROC-curve analysis also revealed the somewhat lesser accuracies of either CD3+ or γδ+ IEL counts. Current official guidelines seem to be somewhat inadequate in clearly defining the spectrum of gluten-induced mucosal pathologies and how they could be optimally interpreted, as well as in promoting the ideal manner for physicians and pathologists to interact in interpreting intestinal mucosae submitted for analysis. Future trends should incorporate 3-D printing and computerised modelling in order to exemplify the subtle micro-anatomical features associated with the crypt-villus interzone. The latter needs precise delineation with use of mRNA in-section assays for brush border enzymes such as alkaline phosphate and esterase. Other additional approaches are needed to facilitate recognition and interpretation of the features of this important inter-zone, such as wells, basins and hypertrophic alterations in the size of inter-villous ridges. The 3-D computerised models could considerably expand our understandings of the microvasculature and its changes—in relation both to crypt hypertrophy, in addition to the partial attrition and subsequent regrowth of villi from the inter-villous ridges during the flattening and recovery processes, respectively.
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Vi Lier Goh, Werlin SL. Discovery of Gluten as the Injurious Component in Celiac Disease. Nutr Clin Pract 2017; 26:160-2. [DOI: 10.1177/0884533611399775] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Vi Lier Goh
- From the Medical College of Wisconsin, Milwaukee, Wisconsin,
vgoh@mcw .edu
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36
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Stein R, Katz D. Celiac Disease. FOODBORNE DISEASES 2017:475-526. [DOI: 10.1016/b978-0-12-385007-2.00024-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dubey A, Sharma D, Singh N, Khan M, Maggo S, Keisham R. Celiac disease: Confounding presentations of Jeopardy in Indians. JOURNAL OF MEDICAL SCIENCES 2017. [DOI: 10.4103/jmedsci.jmedsci_15_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Abstract
PURPOSE OF REVIEW A new syndrome responding to gluten-free diet and defined non-celiac gluten sensitivity entered the spectrum of gluten-related disorders, together with celiac disease and wheat allergy. However, its definition, prevalence, diagnosis, pathogenesis, treatment, and follow up are still controversial. The purpose of the review is to summarize the evidence and problems emerging from the current literature. RECENT FINDINGS Direct implication of gluten in the onset of symptoms is often unproved as a low fermentable oligo-, di- and mono-saccharides and polyols diet or other components of cereals as wheat amylase trypsin inhibitor could be similarly involved. To date, no specific biomarkers or histological abnormalities confirm diagnosis, and only the self-reported response to gluten-free diet as well as a positive double blind placebo-gluten challenge characterizes these non-celiac, non-wheat allergic patients. Critical revision of published studies can offer practical indications in approaching this clinical topic and useful suggestions to standardize scientific researches.
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Affiliation(s)
- Maria Teresa Bardella
- Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122, Milan, Italy.
- , Via Giambologna, 1 - 20136, Milan, Italy.
| | - Luca Elli
- Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122, Milan, Italy
| | - Francesca Ferretti
- Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122, Milan, Italy
- Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122, Milan, Italy
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Gilissen LJWJ, van der Meer IM, Smulders MJM. Why Oats Are Safe and Healthy for Celiac Disease Patients. Med Sci (Basel) 2016; 4:medsci4040021. [PMID: 29083384 PMCID: PMC5635790 DOI: 10.3390/medsci4040021] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 11/09/2016] [Accepted: 11/21/2016] [Indexed: 12/12/2022] Open
Abstract
The water-insoluble storage proteins of cereals (prolamins) are called “gluten” in wheat, barley, and rye, and “avenins” in oat. Gluten can provoke celiac disease (CD) in genetically susceptible individuals (those with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 serotypes). Avenins are present at a lower concentration (10%–15% of total protein content) in oat as compared to gluten in wheat (80%–85%). The avenins in the genus Avena (cultivated oat as well as various wild species of which gene bank accessions were analyzed) are free of the known CD immunogenic epitopes from wheat, barley, and rye. T cells that recognize avenin-specific epitopes have been found very rarely in CD patients. CD patients that consume oats daily do not show significantly increased levels of intraepithelial lymphocyte (EIL) cells. The safety and the positive health effects of the long-term inclusion of oats in the gluten-free diet have been confirmed in long-term studies. Since 2009 (EC 41/2009) and 2013 (FDA) oat products may be sold as gluten-free in several countries provided a gluten contamination level below 20 ppm. Introduction of oats in the gluten-free diet of celiac patients is advised after the recovery of the intestine. Health effects of oat consumption are reflected in European Food Safety Authority (EFSA)- and Food and Drug Administration (FDA)-approved health claims. Oats can form a healthy, nutritious, fiber-rich, and safe complement to the gluten-free diet.
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Affiliation(s)
- Luud J W J Gilissen
- Wageningen University & Research, Bioscience, 6700 AA Wageningen, The Netherlands.
| | | | - Marinus J M Smulders
- Wageningen University & Research, Plant Breeding, 6700 AA Wageningen, The Netherlands.
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Aranda EA, Araya M. Tratamiento de la enfermedad celíaca. ¿Cómo medir adherencia a la dieta libre de gluten? ACTA ACUST UNITED AC 2016; 87:442-448. [DOI: 10.1016/j.rchipe.2016.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 12/17/2015] [Accepted: 01/18/2016] [Indexed: 12/27/2022]
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Does Increased Duodenal Intraepithelial Lymphocytosis Always Equate With Marsh 1 Lesion? J Clin Gastroenterol 2016; 50:613-4. [PMID: 27509445 DOI: 10.1097/mcg.0000000000000562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Donnelly SC, Šuligoj T, Ellis HJ, Ciclitira PJ. Identification of coeliac disease triggering glutenin peptides in adults. Scand J Gastroenterol 2016; 51:819-26. [PMID: 26911209 DOI: 10.3109/00365521.2016.1150504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Coeliac disease affects approximately 1% of Northern American and European populations. It is caused by an inappropriate immune response to dietary gluten. Gluten comprises of two major protein fractions: gliadins and glutenins. Glutenins have recently been found to be toxic to coeliac individuals. Proliferation assays suggest in some but not all paediatric coeliac individuals there may be immunological stimulation with high molecular weight (HMW) glutenins. Less evidence pertains to low molecular weight (LMW) glutenins. The aim is to assess adaptive, T-cell driven, and innate immune response in adult coeliac individuals towards HMW glutenin peptide, glut04, and LMW glutenin peptide, glt156. MATERIALS AND METHODS Coeliac patients were recruited attending endoscopy for routine monitoring. Adaptive immune response towards glut04 and glt156 was measured by proliferation assays and measurement of interferon-γ secretion in 28 T-cell lines. The innate immune response was assessed by measurement of enterocyte cell height (ECH) in coeliac small intestinal biopsies following overnight incubation in organ culture chambers in a further nine individuals. RESULTS There were 3/28 and 2/28 positive proliferation results using gluten-sensitive T-cells with glut04 and glt156, respectively. All coeliac biopsies tested in organ culture chambers demonstrated clear reduction in ECH with peptic-tryptic digest of whole industrial gluten, glut04 and glt156 when compared to negative control ovalbumin (p < 0.005). Three individuals had both T-cell and organ culture study data. Their proliferation assays showed no stimulation of the T-cells. CONCLUSIONS This study demonstrates glutenin epitopes glut04 and glt156, while minor T-cell epitopes, are important in their ability to trigger the innate immune response.
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Affiliation(s)
- Suzanne C Donnelly
- a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK
| | - Tanja Šuligoj
- a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK
| | - H Julia Ellis
- a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK
| | - Paul J Ciclitira
- a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK
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Affiliation(s)
- Geoffrey Holmes
- Emeritus Consultant Gastroenterologist, The Royal Derby Hospital, Derbyshire, UK.
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45
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Mårild K, Ludvigsson JF, Størdal K. Current evidence on whether perinatal risk factors influence coeliac disease is circumstantial. Acta Paediatr 2016; 105:366-75. [PMID: 26258529 DOI: 10.1111/apa.13150] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 06/11/2015] [Accepted: 08/05/2015] [Indexed: 12/16/2022]
Abstract
UNLABELLED Coeliac disease is triggered by an interplay of environmental and genetic factors and is one of the most prevalent autoimmune diseases in children, occurring in about 1% of Europeans. Over the last few decades, there has been a growing interest in the role of the perinatal environment in coeliac disease and this review discusses the growing body of literature on coeliac disease and perinatal risk factors. CONCLUSION There is still only circumstantial evidence that the perinatal environment influences coeliac disease development. Large-scale cohort studies and emerging scientific concepts, such as epigenetics, may help us establish the role of these environmental factors.
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Affiliation(s)
- Karl Mårild
- Division of Epidemiology; Norwegian Institute of Public Health; Oslo Norway
- Department of Medical Epidemiology & Biostatistics; Karolinska Institutet; Stockholm Sweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology & Biostatistics; Karolinska Institutet; Stockholm Sweden
- Department of Pediatrics; Örebro University Hospital; Örebro Sweden
| | - Ketil Størdal
- Division of Epidemiology; Norwegian Institute of Public Health; Oslo Norway
- Department of Pediatrics; Østfold Hospital Trust; Fredrikstad Norway
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Hadjivassiliou M, Sanders DS, Aeschlimann D. The Neuroimmunology of Gluten Intolerance. NEURO-IMMUNO-GASTROENTEROLOGY 2016:263-285. [DOI: 10.1007/978-3-319-28609-9_15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sams A, Hawks J. Celiac disease as a model for the evolution of multifactorial disease in humans. Hum Biol 2015; 86:19-36. [PMID: 25401984 DOI: 10.3378/027.086.0102] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2013] [Indexed: 11/05/2022]
Abstract
Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models of disease. Specifically, we conclude that the set of loci underlying CD risk did not cohesively evolve as a response to a single past selection event such as the development of agriculture. Rather, deterministic and stochastic evolutionary processes have both contributed to the present distribution of variation in CD risk loci. Selection has shaped some components of this network, but this selection appears to have occurred at different points in the past. Other parts of the CD risk network have likely arisen due to stochastic processes such as genetic drift.
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Affiliation(s)
- Aaron Sams
- Cornell University, Ithaca, New York, USA
| | - John Hawks
- University of Wisconsin-Madison, Madison, Wisconsin, USA
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48
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Dieli-Crimi R, Cénit MC, Núñez C. The genetics of celiac disease: A comprehensive review of clinical implications. J Autoimmun 2015; 64:26-41. [DOI: 10.1016/j.jaut.2015.07.003] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 07/01/2015] [Indexed: 02/09/2023]
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Abstract
Celiac disease (CD) is an immune-mediated disease characterized by permanent gastrointestinal tract sensitivity to gluten in genetically predisposed individuals. It has varied clinical manifestations, ranging from gastrointestinal to extraintestinal, including neurological, skin, reproductive and psychiatric symptoms, which makes its diagnosis difficult and challenging. Known neurological manifestations of CD include epilepsy with or without occipital calcification, attention deficit hyperactivity disorder and ataxia, headache, neuropathies and behavior disorders. We present the case of a 14-year-old female with headaches and blurred vision for 1 year; she was noted to have papilledema on ophthalmic examination with increased cerebrospinal fluid opening pressure on lumber puncture and was diagnosed as a case of pseudotumor cerebri (PTC). Meanwhile her workup for chronic constipation revealed elevated tissue transglutaminase IgA and antiendomysial IgA antibodies. Upper gastrointestinal endoscopy with duodenal biopsy confirmed the diagnosis of CD. The patient was started on a gluten-free diet, leading to resolution of not only gastrointestinal symptoms but also to almost complete resolution of symptoms of PTC. This report describes the correlation of CD and PTC as its neurological manifestation.
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Affiliation(s)
- Uzma Rani
- State University of New York Upstate Medical University, Syracuse, N.Y., USA
| | - Aamer Imdad
- State University of New York Upstate Medical University, Syracuse, N.Y., USA
| | - Mirza Beg
- State University of New York Upstate Medical University, Syracuse, N.Y., USA
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Lundin KEA, Qiao SW, Snir O, Sollid LM. Coeliac disease - from genetic and immunological studies to clinical applications. Scand J Gastroenterol 2015; 50:708-17. [PMID: 25846940 DOI: 10.3109/00365521.2015.1030766] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Coeliac disease is a common and important gastrointestinal disease. It affects at least 1%, most Western European populations and in Nordic countries it is even more frequent. It is strongly associated with certain Human Leukocyte Antigen-DQ genes and triggered by ingestion of wheat gluten and related cereals from rye and barley. The diagnosis relies on a combination of clinical signs, serology and small intestinal biopsy. Work during the last couple of decades has shown that gluten-specific, Human Leukocyte Antigen-DQ-restricted T-cells in the intestinal mucosa are of paramount importance in the disease process. The gluten peptides are chemically modified by the endogenous enzyme transglutaminase 2, the same enzyme that serves as target in today's sensitive serological tests for coeliac disease. The increasing knowledge on the disease process allows for development of improved diagnosis, patient care and new treatment modalities.
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Affiliation(s)
- Knut E A Lundin
- Department of Gastroenterology, Oslo University Hospital-Rikshospitalet , Oslo , Norway
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