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Caproni M, Capone M, Rossi MC, Santarlasci V, Maggi L, Mazzoni A, Rossettini B, Renzi D, Quintarelli L, Bianchi B, Ninci A, Lami G, Calabrò A, Cosmi L, Annunziato F, Liotta F. T Cell Response Toward Tissue-and Epidermal-Transglutaminases in Coeliac Disease Patients Developing Dermatitis Herpetiformis. Front Immunol 2021; 12:645143. [PMID: 33959126 PMCID: PMC8093623 DOI: 10.3389/fimmu.2021.645143] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/24/2021] [Indexed: 12/19/2022] Open
Abstract
The reason why only few coeliac patients develop the cutaneous manifestation of the disease, named dermatitis herpetiformis (DH), is still unknown. Epidermal transglutaminase (TG3) has been described as the main autoantigen of humoral immunity in DH but the mechanisms leading to this autoimmune response remain obscure. Here we characterized T cells from skin, gut and peripheral blood of DH and coeliac disease (CD) patients, evaluated the impact of the gluten-free diet on circulating T lymphocytes’ phenotype and investigated antigen specific T cell response toward epidermal and tissue transglutaminase (TG2). DH patients showed an increased frequency of skin-derived T cells producing TNFα when compared to CD patients. Moreover, circulating T cells producing TNFα and IL-17A positively correlated with clinical score of skin disease activity and decreased after gluten-free diet. Finally, TG2 and TG3-specific T cells resulted more reactive to antigens stimulation in DH patients and showed cross reactivity toward the two autoantigens in both the group of patients. Our data suggest a role of TNFα and IL-17A producing cells in the development of DH and, for the first time, show the existence of a crossed T cell response toward the two transglutaminases isoforms, thus suggesting new insights on T cells role in skin damage.
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Affiliation(s)
- Marzia Caproni
- Rare Diseases Unit, Section of Dermatology, Department of Health Sciences, USL Toscana Centro, University of Florence, European Reference Network-Skin Member, Florence, Italy
| | - Manuela Capone
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Maria Caterina Rossi
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Veronica Santarlasci
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Laura Maggi
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Alessio Mazzoni
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Beatrice Rossettini
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Daniela Renzi
- Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Lavinia Quintarelli
- Rare Diseases Unit, Section of Dermatology, Department of Health Sciences, USL Toscana Centro, University of Florence, European Reference Network-Skin Member, Florence, Italy
| | - Beatrice Bianchi
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Alessandra Ninci
- Medical Specialization School of Hygiene and Preventive Medicine, University of Florence, Florence, Italy
| | - Gabriele Lami
- Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Antonio Calabrò
- Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Lorenzo Cosmi
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Francesco Annunziato
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
| | - Francesco Liotta
- Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
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Wolf J, Willscher E, Loeffler-Wirth H, Schmidt M, Flemming G, Zurek M, Uhlig HH, Händel N, Binder H. Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies. Int J Mol Sci 2021; 22:ijms22052551. [PMID: 33806322 PMCID: PMC7961974 DOI: 10.3390/ijms22052551] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 12/11/2022] Open
Abstract
Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups-a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease.
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Affiliation(s)
- Johannes Wolf
- Department of Laboratory Medicine at Hospital “St. Georg” Leipzig, 04129 Leipzig, Germany;
- Immuno Deficiency Centre Leipzig (IDCL) at Hospital St. Georg Leipzig, Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiency Diseases, 04129 Leipzig, Germany
| | - Edith Willscher
- IZBI, Interdisciplinary Centre for Bioinformatics, University Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany; (E.W.); (H.L.-W.); (M.S.)
| | - Henry Loeffler-Wirth
- IZBI, Interdisciplinary Centre for Bioinformatics, University Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany; (E.W.); (H.L.-W.); (M.S.)
| | - Maria Schmidt
- IZBI, Interdisciplinary Centre for Bioinformatics, University Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany; (E.W.); (H.L.-W.); (M.S.)
| | - Gunter Flemming
- Paediatric Gastroenterology Unit, University Hospital for Children and Adolescents, 04103 Leipzig, Germany;
| | - Marlen Zurek
- Children’s Hospital of the Clinical Centre “Sankt Georg”, 04129 Leipzig, Germany; (M.Z.); (N.H.)
| | - Holm H. Uhlig
- Translational Gastroenterology Unit, Oxford NIHR Biomedical Research Centre, Experimental Medicine, Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX4 2PG, UK;
| | - Norman Händel
- Children’s Hospital of the Clinical Centre “Sankt Georg”, 04129 Leipzig, Germany; (M.Z.); (N.H.)
| | - Hans Binder
- IZBI, Interdisciplinary Centre for Bioinformatics, University Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany; (E.W.); (H.L.-W.); (M.S.)
- Correspondence:
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Ramírez-Sánchez AD, Tan IL, Gonera-de Jong B, Visschedijk MC, Jonkers I, Withoff S. Molecular Biomarkers for Celiac Disease: Past, Present and Future. Int J Mol Sci 2020; 21:E8528. [PMID: 33198309 PMCID: PMC7697360 DOI: 10.3390/ijms21228528] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/10/2020] [Indexed: 12/19/2022] Open
Abstract
Celiac disease (CeD) is a complex immune-mediated disorder that is triggered by dietary gluten in genetically predisposed individuals. CeD is characterized by inflammation and villous atrophy of the small intestine, which can lead to gastrointestinal complaints, malnutrition, and malignancies. Currently, diagnosis of CeD relies on serology (antibodies against transglutaminase and endomysium) and small-intestinal biopsies. Since small-intestinal biopsies require invasive upper-endoscopy, and serology cannot predict CeD in an early stage or be used for monitoring disease after initiation of a gluten-free diet, the search for non-invasive biomarkers is ongoing. Here, we summarize current and up-and-coming non-invasive biomarkers that may be able to predict, diagnose, and monitor the progression of CeD. We further discuss how current and emerging techniques, such as (single-cell) transcriptomics and genomics, can be used to uncover the pathophysiology of CeD and identify non-invasive biomarkers.
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Affiliation(s)
- Aarón D. Ramírez-Sánchez
- Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (A.D.R.-S.); (I.L.T.); (I.J.)
| | - Ineke L. Tan
- Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (A.D.R.-S.); (I.L.T.); (I.J.)
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
| | - B.C. Gonera-de Jong
- Department of Pediatrics, Wilhelmina Hospital Assen, 9401 RK Assen, The Netherlands;
| | - Marijn C. Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
| | - Iris Jonkers
- Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (A.D.R.-S.); (I.L.T.); (I.J.)
| | - Sebo Withoff
- Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (A.D.R.-S.); (I.L.T.); (I.J.)
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Taavela J, Viiri K, Popp A, Oittinen M, Dotsenko V, Peräaho M, Staff S, Sarin J, Leon F, Mäki M, Isola J. Histological, immunohistochemical and mRNA gene expression responses in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded duodenal biopsies. BMC Gastroenterol 2019; 19:189. [PMID: 31730447 PMCID: PMC6858741 DOI: 10.1186/s12876-019-1089-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 10/07/2019] [Indexed: 12/26/2022] Open
Abstract
Background There is an unmet need for novel treatments, such as drugs or vaccines, adjunctive to or replacing a burdensome life-long gluten-free diet for coeliac disease. The gold standard for successful treatment is a healed small intestinal mucosa, and therefore, the outcome measures in proof-of-concept studies should be based on evaluation of small intestine biopsies. We here evaluated morphometric, immunohistochemical and messenger RNA (mRNA) expression changes in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded biopsies. Methods Fifteen coeliac disease patients were challenged with 4 g of gluten per day for 10 weeks and 24 non-coeliac patients served as disease controls. A wide array of histological and immunohistochemical staining and mRNA-based gene expression tests (RT-qPCR and RNAseq) were carried out. Results Digital quantitative villous height: crypt depth ratio (VH: CrD) measurements revealed significant duodenal mucosal deterioration in all coeliac disease patients on gluten challenge. In contrast, the Marsh-Oberhuber class worsened in only 80% of coeliac patients. Measuring the intraepithelial CD3+ T-lymphocyte and lamina propria CD138+ plasma cell densities simultaneously proved to be a meaningful new measure of inflammation. Stainings for γδ T cells and IgA deposits, where previously frozen samples have been needed, were successful in PAXgene fixed paraffin-embedded samples. Messenger RNA extraction from the same paraffin-embedded biopsy block was successful and allowed large-scale qRT-PCR and RNAseq analyses for gene expression. Molecular morphometry, using the mRNA expression ratio of villous epithelium-specific gene APOA4 to crypt proliferation gene Ki67, showed a similar significant distinction between paired baseline and post-gluten challenge biopsies as quantitative histomorphometry. Conclusion Rigorous digitally measured histologic and molecular markers suitable for gluten challenge studies can be obtained from a single paraffin-embedded biopsy specimen. Molecular morphometry seems to be a promising new tool that can be used in situations where assessing duodenal mucosal health is of paramount importance. In addition, the diagnostically valuable IgA deposits were now stained in paraffin-embedded specimens making them more accessible in routine clinics.
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Affiliation(s)
- Juha Taavela
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.,Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland
| | - Keijo Viiri
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland
| | - Alina Popp
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.,University of Medicine and Pharmacy "Carol Davila" and National Institute for Mother and Child Health "Alessandrescu-Rusescu", Bucharest, Romania
| | - Mikko Oittinen
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland
| | - Valeriia Dotsenko
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland
| | - Markku Peräaho
- Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland
| | - Synnöve Staff
- Department of Gynaecology and Obstetrics, Tampere University Hospital, Tampere, Finland.,Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jani Sarin
- Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Jilab Inc., Tampere, Finland
| | | | - Markku Mäki
- Department of Paediatrics, Tampere Centre for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland
| | - Jorma Isola
- Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. .,Jilab Inc., Tampere, Finland.
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Imperatore N, Tortora R, De Palma GD, Capone P, Gerbino N, Donetto S, Testa A, Caporaso N, Rispo A. Beneficial effects of gluten free diet in potential coeliac disease in adult population. Dig Liver Dis 2017; 49:878-882. [PMID: 28396103 DOI: 10.1016/j.dld.2017.03.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 03/13/2017] [Accepted: 03/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND To date, potential coeliac disease (PCD) occurring in adults remains an almost unexplored condition. AIMS To explore the prognostic role of Marsh grade in adult PCD patients, and to evaluate the effects of gluten-containing diet (GCD) in asymptomatic PCD patients. METHODS We retrospectively evaluated all consecutive adult PCD patients followed-up for at least 6 years. Patients were divided into: Group A (patients with Marsh 0 histology) and Group B (Marsh 1 patients). Symptomatic patients were started gluten-free diet (GFD), while asymptomatic subjects were kept on GCD and were followed-up. RESULTS 56 PCD patients were enrolled (21 in Group A and 35 in Group B). Forty-three patients were symptomatic and started GFD. Of these, none of 15 patients in Group A and 8 of 28 patients in Group B developed immune-mediated disorders (IMD) during follow-up (P=0.03; OR=4.2). The 13 asymptomatic PCD patients were kept on GCD. During the follow-up, 9 patients developed CD-related symptoms, 6 villous atrophy and 8 IMD. At the end, patients kept on GCD were at higher risk of developing IMD than those following a GFD (61% vs 18%, P=0.03, OR=3.3). CONCLUSIONS Although PCD with normal mucosa seems to be a milder disease, the continuation of GCD places patients at a high risk of developing villous atrophy and IMD compared to commencement of GFD. Adult PCD patients should start GFD even if not symptomatic.
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Affiliation(s)
- Nicola Imperatore
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy.
| | - Raffaella Tortora
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Giovanni Domenico De Palma
- Surgery and Advanced Endoscopy, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Pietro Capone
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Nicolò Gerbino
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Sara Donetto
- Department of Education and Professional Studies, King's College London, London, UK
| | - Anna Testa
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Nicola Caporaso
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
| | - Antonio Rispo
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine "Federico II" of Naples, Italy
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Ciccocioppo R, Kruzliak P, Cangemi GC, Pohanka M, Betti E, Lauret E, Rodrigo L. The Spectrum of Differences between Childhood and Adulthood Celiac Disease. Nutrients 2015; 7:8733-51. [PMID: 26506381 PMCID: PMC4632446 DOI: 10.3390/nu7105426] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Revised: 10/06/2015] [Accepted: 10/12/2015] [Indexed: 02/06/2023] Open
Abstract
An old saying states that ''children are not little adults" and this certainly holds true for celiac disease, as there are many peculiar aspects regarding its epidemiology, diagnosis, clinical presentations, associated diseases, and response to treatment in pediatric compared to adult populations, to such an extent that it merits a description of its own. In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation. In general, the clinical guidelines for diagnosis recommend starting with specific serologic testing in all suspected subjects, including those suffering from extraintestinal related conditions, and performing upper endoscopy with appropriate biopsy sampling of duodenal mucosa in case of positivity. The latter may be omitted in young patients showing high titers of anti-transglutaminase antibodies. The subsequent management of a celiac patient differs substantially depending on the age at diagnosis and should be based on the important consideration that this is a lifelong condition.
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Affiliation(s)
- Rachele Ciccocioppo
- Rachele Ciccocioppo, Center for the Study and Cure of Celiac Disease, Clinica Medica I, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, 19-27100 Pavia, Italy.
| | - Peter Kruzliak
- International Clinical Research Center, St. Anne's University Hospital and Masaryk University, 65691 Brno, Czech Republic.
| | - Giuseppina C Cangemi
- Rachele Ciccocioppo, Center for the Study and Cure of Celiac Disease, Clinica Medica I, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, 19-27100 Pavia, Italy.
| | - Miroslav Pohanka
- Faculty of Military Health Sciences, University of Defence, Trebešská 1575-500 01 Hradec Kralove, Czech Republic.
- Department of Geology and Pedology, Faculty of Forestry and Wood Technology, Mendel University in Brno, 61300 Brno, Czech Republic.
| | - Elena Betti
- Rachele Ciccocioppo, Center for the Study and Cure of Celiac Disease, Clinica Medica I, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, 19-27100 Pavia, Italy.
| | - Eugenia Lauret
- Gastroenterology Unit, Hospital Universitario Central de Asturias, 33000 Oviedo, Spain.
| | - Luis Rodrigo
- Gastroenterology Unit, Hospital Universitario Central de Asturias, 33000 Oviedo, Spain.
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Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy. Mediators Inflamm 2015; 2015:738563. [PMID: 26346822 PMCID: PMC4540995 DOI: 10.1155/2015/738563] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 07/05/2015] [Indexed: 01/27/2023] Open
Abstract
Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa.
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Garg K, Gupta RK. What a practitioner needs to know about celiac disease? Indian J Pediatr 2015; 82:145-51. [PMID: 25172576 DOI: 10.1007/s12098-014-1544-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Accepted: 07/14/2014] [Indexed: 02/07/2023]
Abstract
Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and is characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes and enteropathy. CD is triggered by wheat gluten and related prolamines in barley and rye. Worldwide, the disease affects approximately 1 % of the general population. Clinical features of CD vary considerably. Intestinal symptoms are more common in young children. In older children extra intestinal manifestations affecting almost all organs are seen. IgA tTG antibody, upper GI endoscopy with histological analysis of multiple biopsies of the duodenum and in selected cases HLA DQ2 and DQ8 positivity and endomysial antibodies (EMA) are needed for diagnosis. Currently, the only treatment for CD is a life-long gluten-free diet (GFD). Strict avoidance of wheat, rye, barley and their derivatives will result in intestinal healing and relief of symptoms for the majority of individuals with CD. The GFD is simple in principle, however, completely eliminating all foods and ingredients containing wheat, rye, barley, and most commercial oats can be very challenging. Newly diagnosed CD children should undergo testing and treatment for micronutrient deficiencies specially iron, folic acid, vitamin D, and vitamin B12. Long-term monitoring and follow up of patients with CD is necessary.
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Affiliation(s)
- Kapil Garg
- Department of Pediatrics, SMS Medical College, Jaipur, Rajasthan, 302004, India,
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Tack GJ, van de Water JMW, Bruins MJ, Kooy-Winkelaar EMC, van Bergen J, Bonnet P, Vreugdenhil ACE, Korponay-Szabo I, Edens L, von Blomberg BME, Schreurs MWJ, Mulder CJ, Koning F. Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study. World J Gastroenterol 2013; 19:5837-47. [PMID: 24124328 PMCID: PMC3793137 DOI: 10.3748/wjg.v19.i35.5837] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 10/05/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients.
METHODS: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint.
RESULTS: In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their mucosa showed an increase of two Marsh steps after the safety phase, yet with undetectable serum antibodies, while 14 patients were considered histologically stable on gluten with AN-PEP. Also after the efficacy phase, no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo. In the seven patients receiving AN-PEP, one patient showed increased and one showed decreased IgA-tTG deposits.
CONCLUSION: AN-PEP appears to be well tolerated. However, the primary endpoint was not met due to lack of clinical deterioration upon placebo, impeding an effect of AN-PEP.
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10
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Cooper SEJ, Kennedy NP, Mohamed BM, Abuzakouk M, Dunne J, Byrne G, McDonald G, Davies A, Edwards C, Kelly J, Feighery CF. Immunological indicators of coeliac disease activity are not altered by long-term oats challenge. Clin Exp Immunol 2013; 171:313-8. [PMID: 23379438 DOI: 10.1111/cei.12014] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/11/2012] [Indexed: 12/22/2022] Open
Abstract
Coeliac disease is a gluten-sensitive enteropathy that develops in genetically susceptible individuals. The disease exhibits many features of an autoimmune disorder. These include the production of highly specific anti-endomysial autoantibodies directed against the enzyme tissue transglutaminase. It is well accepted that wheat-, barley- and rye-based foods should be excluded in the gluten-free diet. Although several studies report that oats ingestion is safe in this diet, the potential toxicity of oats remains controversial. In the current study, 46 coeliac patients ingested oats for 1 year and were investigated for a potential immunogenic or toxic effect. Stringent clinical monitoring of these patients was performed and none experienced adverse effects, despite ingestion of a mean of 286 g of oats each week. Routine histological analysis of intestinal biopsies showed improvement or no change in 95% of the samples examined. Furthermore, tissue transglutaminase expression in biopsy samples, determined quantitatively using the IN Cell Analyzer, was unchanged. Employing immunohistochemistry, oats ingestion was not associated with changes in intraepithelial lymphocyte numbers or with enterocyte proliferation as assessed by Ki-67 staining. Finally, despite the potential for tissue transglutaminase to interact with oats, neither endomysial nor tissue transglutaminase antibodies were generated in any of the patients throughout the study. To conclude, this study reaffirms the lack of oats immunogenicity and toxicity to coeliac patients. It also suggests that the antigenic stimulus caused by wheat exposure differs fundamentally from that caused by oats.
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Affiliation(s)
- S E J Cooper
- Department of Immunology, St James's Hospital and Trinity College Dublin, Dublin, Ireland
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Bürgin-Wolff A, Mauro B, Faruk H. Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests. BMC Gastroenterol 2013; 13:19. [PMID: 23343249 PMCID: PMC3563615 DOI: 10.1186/1471-230x-13-19] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 01/14/2013] [Indexed: 12/14/2022] Open
Abstract
Background The objective of this study was to compare celiac disease (CD)– specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. Methods This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. Results Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. Conclusion Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.
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Gujral N, Freeman HJ, Thomson ABR. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol 2012; 18:6036-59. [PMID: 23155333 PMCID: PMC3496881 DOI: 10.3748/wjg.v18.i42.6036] [Citation(s) in RCA: 397] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 07/27/2012] [Accepted: 08/03/2012] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.
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Ravelli A, Villanacci V. Tricks of the trade: How to avoid histological pitfalls in celiac disease. Pathol Res Pract 2012; 208:197-202. [PMID: 22417775 DOI: 10.1016/j.prp.2012.01.008] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Revised: 12/30/2011] [Accepted: 01/30/2012] [Indexed: 02/08/2023]
Abstract
Currently, the diagnosis of celiac disease (CD) is based upon the combination of raised serum anti-tissue transglutaminase or anti-endomysial antibodies and the presence of histological alterations of variable degree in the duodenal mucosa. Interpretation of duodenal biopsies is subjected to a number of variables, and the lack of standardization may cause diagnostic controversy or even misdiagnosis. The aim of this overview is to solicit a standardization of the procedures of biopsy taking, orientation, processing, staining and interpretation in order to avoid or minimize misinterpretation of duodenal biopsies. Based on a literature review and extensive personal experience, the appropriate methodology of duodenal biopsy taking, orientation, fixation, processing, staining and interpretation was thoroughly reviewed, and the most common and relevant errors and artifacts were identified. To maximize the diagnostic yield of duodenal biopsy in CD, multiple specimens are best taken from different sites of the duodenum during endoscopy, and careful visual inspection of the duodenal mucosa may help identify abnormalities related to villous atrophy. Biopsy handling and orientation are of utmost importance to avoid artifacts that may impair the pathologist's ability to detect pathology and normality. Immunostaining with anti-CD3 monoclonal antibody should be carried out, and a simplified histological classification may help distinguish atrophic from non-atrophic stages of CD enteropathy. Meticulous attention to biopsy orientation, handling and processing - together with the knowledge of the most common histological artifacts - is necessary to avoid a wrong histological interpretation which, in turn, may lead to misdiagnosis in CD.
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Affiliation(s)
- Alberto Ravelli
- Gastroenterology and GI Endoscopy, University Department of Pediatrics, Children's Hospital, Brescia, Italy. alberto
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Mubarak A, Nikkels P, Houwen R, Ten Kate F. Reproducibility of the histological diagnosis of celiac disease. Scand J Gastroenterol 2011; 46:1065-73. [PMID: 21668407 DOI: 10.3109/00365521.2011.589471] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE A small intestinal biopsy is considered to be the gold standard for the diagnosis of celiac disease (CD). However, the assessment of small intestinal histology may vary between pathologists. Our aim was, therefore, to determine the interobserver variability in the histological diagnosis of CD. MATERIAL AND METHODS Biopsy specimens of 297 pediatric patients suspected of having CD were revised by a single experienced pathologist and compared to the original reports. Mucosal changes were scored using the Marsh classification. In patients with a discrepancy in diagnosis, clinical and serological data were used to determine the most probable diagnosis. RESULTS Although the interobserver variability for the Marsh classification was found to be moderate with a Kappa value of 0.486, the Kappa value for the diagnosis reached an almost perfect agreement (0.850). Nevertheless, in 22 patients a different diagnosis was made by the second observer. Interestingly, in this subgroup relatively more biopsies were classified to be of suboptimal quality. Based on clinical presentation, serology and follow-up, 19 of those patients truly had CD. In 14 of them the diagnosis was originally missed by the first observer while five cases were under-diagnosed by the second pathologist. CONCLUSIONS CD can be missed histologically due to assessment variation between pathologists. A final diagnosis of CD should be based on histology, serology as well as response to the diet.
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Affiliation(s)
- Amani Mubarak
- Department of Pediatric Gastroenterology, Wilhelmina Children's hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
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Abstract
OBJECTIVES Small intestinal histology is the criterion standard for the diagnosis of celiac disease (CD). However, results of serological tests such as anti-endomysium antibodies and anti-tissue transglutaminase antibodies (tTGA) are becoming increasingly reliable. This raises the question of whether a small intestinal biopsy is always necessary. The aim of the present study was, therefore, to investigate whether a small intestinal biopsy can be avoided in a selected group of patients. PATIENTS AND METHODS Serology and histological slides obtained from 283 pediatric patients suspected of having CD were examined retrospectively. The response to a gluten-free diet (GFD) in patients with a tTGA level ≥ 100 U/mL was investigated. RESULTS A tTGA level ≥ 100 U/mL was found in 128 of the 283 patients. Upon microscopic examination of the small intestinal epithelium, villous atrophy was found in 124 of these patients, confirming the presence of CD. Three patients had crypt hyperplasia or an increased number of intraepithelial lymphocytes. In 1 patient no histological abnormalities were found. This patient did not respond to a GFD. CONCLUSIONS Pediatric patients with a tTGA level ≥ 100 U/mL in whom symptoms improve upon consuming a GFD may not need a small intestinal biopsy to confirm CD.
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Abstract
OBJECTIVES The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet. METHODS We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology. RESULTS The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance. CONCLUSIONS Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten-free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody.
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Dickey W. Diagnostic immunology in celiac disease. Expert Rev Clin Immunol 2010; 5:471-9. [PMID: 20477043 DOI: 10.1586/eci.09.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Serum autoantibodies to transglutaminase and endomysium are found in the majority of patients with celiac disease, an autoimmune multisystem disorder affecting approximately 1% of Western and Middle-Eastern populations. Detection of these antibodies plays a crucial role in the diagnosis of celiac disease. The aim of this review is to summarize recent publications in this field, with particular focus on the applications and limitations of celiac autoantibody testing in routine clinical practice.
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Affiliation(s)
- William Dickey
- Department of Gastroenterology, Altnagelvin Hospital, Londonderry, Northern Ireland, BT47 6SB, UK.
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Tack GJ, Verbeek WHM, Schreurs MWJ, Mulder CJJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol 2010; 7:204-13. [PMID: 20212505 DOI: 10.1038/nrgastro.2010.23] [Citation(s) in RCA: 173] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Celiac disease is a gluten-sensitive enteropathy that affects people of all ages worldwide. This disease has emerged as a major health-care problem, as advances in diagnostic and screening methods have revealed its global prevalence. Environmental factors such as gluten introduction at childhood, infectious agents and socioeconomic features, as well as the presence of HLA-DQ2 and/or HLA-DQ8 haplotypes or genetic variations in several non-HLA genes contribute to the development of celiac disease. Growing insight into the variable clinical and histopathological presentation features of this disease has opened new perspectives for future research. A strict life-long gluten-free diet is the only safe and efficient available treatment, yet it results in a social burden. Alternative treatment modalities focus on modification of dietary components, enzymatic degradation of gluten, inhibition of intestinal permeability and modulation of the immune response. A small group of patients with celiac disease (2-5%), however, fail to improve clinically and histologically upon elimination of dietary gluten. This complication is referred to as refractory celiac disease, and imposes a serious risk of developing a virtually lethal enteropathy-associated T-cell lymphoma.
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Affiliation(s)
- Greetje J Tack
- Department of Gastroenterology and Hepatology, VU University Medical Center, P. O. Box 7057, 1007 MB Amsterdam, The Netherlands.
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Symposium 1: Joint BAPEN and British Society of Gastroenterology Symposium on ‘Coeliac disease: basics and controversies’ Coeliac disease in the twenty-first century. Proc Nutr Soc 2009; 68:234-41. [DOI: 10.1017/s0029665109001414] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting ⩾1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40–60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow ‘once and for all’ exclusion. In conclusion, an increasing proportion of patients with CD do not meet the ‘classic’ picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.
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Kurppa K, Collin P, Viljamaa M, Haimila K, Saavalainen P, Partanen J, Laurila K, Huhtala H, Paasikivi K, Mäki M, Kaukinen K. Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study. Gastroenterology 2009; 136:816-23. [PMID: 19111551 DOI: 10.1053/j.gastro.2008.11.040] [Citation(s) in RCA: 199] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2008] [Revised: 09/30/2008] [Accepted: 11/13/2008] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS The diagnostic criteria for celiac disease require small-bowel mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal damage develops gradually and patients may evince clinical symptoms before histologic changes appear. Endomysial antibodies are specific in predicting forthcoming villous atrophy. We hypothesized that patients with mild enteropathy but positive endomysial antibodies benefit from a gluten-free diet (GFD) similarly to patients with more severe enteropathy. METHODS Small-bowel endoscopy together with clinical evaluations was performed in all together 70 consecutive adults with positive endomysial antibodies. Of these, 23 had only mild enteropathy (Marsh I-II) and they were randomized either to continue on a gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and histologic evaluations were repeated. A total of 47 participants had small-bowel mucosal lesions compatible with celiac disease (Marsh III), and these served as disease controls. RESULTS In the gluten-containing diet group (Marsh I-II) the small-bowel mucosal villous architecture deteriorated in all participants, and the symptoms and abnormal antibody titers persisted. In contrast, in the GFD group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and mucosal inflammation diminished equally to celiac controls (Marsh III). When the trial was completed, all participants chose to continue on a life-long GFD. CONCLUSIONS Patients with endomysial antibodies benefit from a GFD regardless of the degree of enteropathy. The diagnostic criteria for celiac disease need re-evaluation: endomysial antibody positivity without atrophy belongs to the spectrum of genetic gluten intolerance, and warrants dietary treatment.
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Affiliation(s)
- Kalle Kurppa
- Paediatric Research Centre, University of Tampere and Tampere University Hospital, Tampere, Finland
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The use of Cellomics to study enterocyte cytoskeletal proteins in coeliac disease patients. Open Life Sci 2008. [DOI: 10.2478/s11535-008-0029-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AbstractCoeliac disease is characterised by inflammation of small intestinal mucosa accompanied by abnormal villous architecture. It is now accepted that some patients with positive coeliac serology tests may have minor mucosal lesions that may not be apparent on routine histopathological analysis. The aim of the study was to perform detailed examination of enterocyte morphology and cytoskeletal structures using a high content analysis technology. Duodenal biopsies from 14 untreated and 10 treated coeliac patients and from 20 non-coeliac controls were examined. Tissue sections from six patients (study group subjects) before and after the development of gluten-sensitive enteropathy were also investigated. Immunohistochemical studies were performed on paraffin-embedded sections using an anti-α-tubulin antibody. Significant differences in enterocyte morphology and intracellular cytoskeletal structures were demonstrated in patients with proven coeliac disease and in the study group subjects. These changes were present in study group biopsies before evidence of enteropathy, as assessed by routine microscopy. This is the first study to demonstrate detailed characteristics of enterocyte morphology in coeliac patients using a high content analysis approach. The use of this technology allows a quantitative analysis of enterocyte intracellular structures from routine biopsy material and permits detection of subtle changes that precede the characteristic histological lesion.
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