{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:29:09Z","timestamp":1787729349083,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004879","name":"Collegio Ghislieri di Pavia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K23DK119584"],"award-info":[{"award-number":["K23DK119584"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Seronegative coeliac disease is poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To study clinical phenotypes and long\u2010term outcomes of seronegative coeliac disease in a multicentre cohort over 20\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seronegative coeliac disease was diagnosed in HLA\u2010DQ2\/DQ8\u2010positive patients with villous atrophy (VA), negative IgA endomysial (EmA), tissue transglutaminase (tTG) and deamidated\u2010gliadin antibodies (DGP), clinical and histological response to a gluten\u2010free diet (GFD), and no alternative causes for VA. In patients with IgA deficiency, coeliac disease was diagnosed through VA, positive IgG EmA\/tTG\/DGP and clinical\/histological response to a GFD (coeliac disease+IgAd). Patients with seropositive coeliac disease served as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 227 patients previously diagnosed with seronegative coeliac disease, true seronegative coeliac disease was confirmed in 84, coeliac disease+IgAd in 48, and excluded in 55. Lack of follow\u2010up duodenal biopsy precluded diagnosing seronegative coeliac disease in 40 patients. 2084 patients with seropositive coeliac disease served as controls. True seronegative coeliac disease had more severe symptoms at diagnosis and a higher risk of complications (HR 10.87, 95% CI 6.11\u201019.33, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and mortality (HR 2.18, 95% CI 1.12\u20104.26, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) than seropositive coeliac disease. There were no differences between true seronegative coeliac disease and coeliac disease+IgAd. On multivariate analysis, age at diagnosis, lack of clinical response to a GFD, true seronegative coeliac disease, coeliac disease+IgAd, and classical presentation predicted complications. Age at diagnosis, complications and absence of clinical response to a GFD predicted mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Seronegative coeliac disease has a more aggressive disease phenotype than seropositive coeliac disease. These data argue against over\u2010reliance on serology for the diagnosis of coeliac disease and support a strict clinical and histologic follow\u2010up in seronegative coeliac disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.16599","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T18:55:34Z","timestamp":1631127334000},"page":"1278-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Clinical classification and long\u2010term outcomes of seronegative coeliac disease: a 20\u2010year multicentre follow\u2010up study"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-7698","authenticated-orcid":false,"given":"Annalisa","family":"Schiepatti","sequence":"first","affiliation":[{"name":"Academic Department of Gastroenterology Royal Hallamshire Hospital  Sheffield UK"},{"name":"Gastroenterology Unit IRCCS Pavia ICS Maugeri University of Pavia  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