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Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Department of Gastroenterology, Palmerston North District Health Board (DHB), Palmerston North 4442, New Zealand. Gastroenterology Unit, Milton Keynes University Hospital, Milton Keynes MK6 5LD, UK. Department of Pathology, Ankara University Medical School, Ankara 06620, Turkey. Oxford & Department of Gastroenterology, Wolfson College, University of Oxford, Luton & Dunstable University Hospital Trust, Bedfordshire LU4 0DZ, UK. Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Spedali Civili, Institute of Pathology, 25100 Brescia, Italy. Palermo, Internal Medicine Unit, Department 'PROMISE', University of Palermo, "V. Cervello Hospital", 90100 Palermo, Italy. Gastroenterology and Liver Diseases Reseach Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran. Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina. Department of Medicine, University of Perugia School of Medicine, 06129 Perugia, Italy. Department of Pathology, Carol Davila University of Medicine & Pharmacy, 050474 Bucharest, Romania. Gastrointestinal Pathology Center of Excellence University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. Department of Pathology, University of Milan-Bicocca, 20900 Monza, Italy. Medical Deptartment, Desio Hospital, 20832 Desio, Italy. Deptartment of Pediatrics, Universita Politecnica delle Marche, 60123 Ancona, Italy. Dipartimento di Medicina, Chirurgia e Odontoiatria, Scuola Medica Salernitana, Università di Salerno Gastroenterologia, 84084 Salerno, Italy. Pathology Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania. Gastroenterology and Pathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK. Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India. Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, 06125 Perugia, Italy. Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14607, USA. Center for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Massachusetts General Hospital, Center for Celiac Research & Treatment, Boston, MA 02114, USA. Anatomic Pathology Unit, Department 'PROMISE', Palermo, University of Palermo, A.O.U. Policlinico "P. Giaccone", 17491 Palermo, Italy. Division of Pathology, Fondazione IRCSS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, 20832 Milan, Italy. Department of Pathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK. Department of Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA. Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA. Molecular Epidemiology & Public Health Laboratory, School of Veterinary Science, Massey University, Palmerston North 4472, New Zealand. Dudley Group NHS Foundation Trust, Birmingham City University, Birmingham B5 5JU, UK. Weill Cornell Medicine, New York, NY 10075, USA. Luton Dunstable University Hospital, Gastroenterology, Luton LU4 0DZ, UK. Department of Internal Medicine, Tampere University Hospital, 33100 Tampere, Finland. Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland. Department of Histopathology, Royal Wolverhampton NHS Trust, Newcross Hospitals, Wolverhempton WV10 0QP, UK. Department of Gastroenterology, Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India. Haematology Unit, Milton Keynes University Hospital, Milton Keynes MK6 5LD, UK. Institute of Food Sciences-CNR, Immuno-Morphology, 83100 Avellino, Italy. Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran. Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1081 HV Amsterdam, The Netherlands. Department of Experimental and Clinical Sciences, University of Brescia, 25100 Brescia, Italy. Central Finland Central Hospital, 33520 Jyväskylä, Finland. Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy. Department of Anatomical Pathology, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia. College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.

Nutrients. 2022;(12)
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Abstract

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

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Publication Type : Multicenter Study

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