{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:26:21Z","timestamp":1780467981151,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007365","name":"Fondazione IRCCS Policlinico San Matteo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pathological correlates of potential autoimmune gastritis (AIG), defined by anti-parietal cell antibody (PCA) positivity in the absence of gastric atrophy, have never been described. We herein aimed to assess intraepithelial lymphocyte (IEL) infiltration in gastric corpus of AIG patients. From 2000 to 2021, among 53 potential AIG patients, we focused on nine (median age 61 years, IQR 53-82; four females) who subsequently developed overt AIG. IEL infiltration of the oxyntic mucosa was assessed before and after developing overt AIG by measuring deep and superficial CD3+ IEL. AIG patients with different degrees of corpus atrophy, healthy controls (HC), active H. pylori gastritis, celiac disease (CD), and Hashimoto\u2019s thyroiditis patients were included as controls. Of note, deep, but not superficial, CD3+ IEL count was higher (p&amp;lt;0.001) in potential AIG compared to HC and H. pylori gastritis. Deep CD3+ IEL infiltration did not change before or after the evolution into atrophy (median 9.6, IQR 8.8-12.4, vs 11.3, IQR 9.4-12.9). No difference was found in deep CD3+ IEL infiltration among potential, mild, and severe AIG, and compared to Hashimoto\u2019s thyroiditis or CD. A deep CD3+ IEL cut-off of &amp;gt;7\/100 epithelial cells allowed discrimination of any AIG stage and severity (AUC=0.842). We conclude that an increased deep CD3+ IEL infiltration of the oxyntic mucosa could represent a marker of potential AIG. Prospective studies including a larger number of potential AIG patients are needed.<\/jats:p>","DOI":"10.3389\/fimmu.2022.866167","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T07:22:29Z","timestamp":1651648949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Increase of Deep Intraepithelial Lymphocytes in the Oxyntic Mucosa of Patients With Potential and Overt Autoimmune Gastritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Marco Vincenzo","family":"Lenti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vanoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Miceli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Arpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Soriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Capuano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Aronico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Coppola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pasini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Luinetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Paulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Klersy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino Roberto","family":"Corazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Sabatino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41572-020-0187-8","article-title":"Autoimmune Gastritis","volume":"6","author":"Lenti","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.08.011","article-title":"The Changing Face of Chronic Autoimmune Atrophic Gastritis: An Updated Comprehensive Perspective","volume":"18","author":"Massironi","year":"2019","journal-title":"Autoimmun Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930201)71:3<745::AID-CNCR2820710316>3.0.CO;2-1","article-title":"Pernicious Anemia and Subsequent Cancer. A Population-Based Cohort Study","volume":"71","author":"Hsing","year":"1993","journal-title":"Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.018","article-title":"Common Features of Patients With Autoimmune Atrophic Gastritis","volume":"10","author":"Miceli","year":"2012","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/17562848211038771","article-title":"Autoimmune Gastritis, With or Without Pernicious Anemia: Epidemiology, Risk Factors, and Clinical Management","author":"Rustgi","year":"2021","journal-title":"Therap Adv Gastroenterol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.08.006","article-title":"Autoantibodies to Parietal Cells as Predictors of Atrophic Body Gastritis: A Five-Year Prospective Study in Patients With Autoimmune Thyroid Diseases","volume":"10","author":"Tozzoli","year":"2010","journal-title":"Autoimmun Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/BF03347456","article-title":"Serum Autoimmune Gastritis Markers, Pepsinogen I and Parietal Cell Antibodies, in Patients With Type 1 Diabetes Mellitus: A 5-Year Prospective Study","volume":"34","author":"Alonso","year":"2011","journal-title":"J Endocrinol Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1995.0009","article-title":"Associated Autoimmunity in Addison\u2019s Disease","volume":"8","author":"Zelissen","year":"1995","journal-title":"J Autoimmun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000199325","article-title":"Prevalence of Autoimmune Atrophic Gastritis in Vitiligo","volume":"34","author":"Zauli","year":"1986","journal-title":"Digestion"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15317","article-title":"Determinants of Diagnostic Delay in Autoimmune Atrophic Gastritis","volume":"50","author":"Lenti","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15540","article-title":"Natural History of Autoimmune Atrophic Gastritis: A Prospective, Single Centre, Long-Term Experience","volume":"50","author":"Miceli","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06656-x","article-title":"Impaired Quality of Life in Patients With Autoimmune Atrophic Gastritis","volume":"66","author":"Miceli","year":"2021","journal-title":"Dig Dis Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2016.1275771","article-title":"The Challenging Diagnosis of Autoimmune Atrophic Gastritis","volume":"52","author":"Lenti","year":"2017","journal-title":"Scand J Gastroenterol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.21187","article-title":"H(+), K(+)-Atpase (Proton Pump) is the Target Autoantigen of Th1-Type Cytotoxic T Cells in Autoimmune Gastritis","volume":"120","author":"D\u2019Elios","year":"2001","journal-title":"Gastroenterology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.08.004","article-title":"New Insights Into Immune Mechanisms Underlying Autoimmune Diseases of the Gastrointestinal Tract","volume":"14","author":"Di Sabatino","year":"2015","journal-title":"Autoimmun Rev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60254-3","article-title":"Coeliac Disease","volume":"373","author":"Di Sabatino","year":"2009","journal-title":"Lancet"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqy065","article-title":"Mid- and Deep-Zone Gastritis: A Histologic Pattern Associated With Autoimmune Disease But Distinct From Autoimmune Atrophic Gastritis","volume":"150","author":"Speck","year":"2018","journal-title":"Am J Clin Pathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199610000-00001","article-title":"Classification and Grading of Gastritis. The Updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994","volume":"20","author":"Dixon","year":"1996","journal-title":"Am J Surg Pathol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1159\/000199786","article-title":"Histopathological Classification of Nonantral Gastric Endocrine Growths in Man","volume":"41","author":"Solcia","year":"1988","journal-title":"Digestion"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2002.01301.x","article-title":"Gastric Mucosal Atrophy: Interobserver Consistency Using New Criteria for Classification and Grading","volume":"16","author":"Rugge","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"B21","volume-title":"Gastritis and Metaplasia: Precursors of Gastric Neoplasms in WHO Classification of Tumours","author":"Rugge","year":"2019"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2021.10.001","article-title":"Time Course and Risk Factors of Evolution From Potential to Overt Autoimmune Gastritis","author":"Lenti","year":"2021","journal-title":"Dig Liver Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.101","article-title":"Autoimmune Atrophic Gastritis\u2013Pathogenesis, Pathology and Management","volume":"10","author":"Neumann","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880499","article-title":"Autoimmune Gastritis: Distinct Histological and Immunohistochemical Findings Before Complete Loss of Oxyntic Glands","volume":"15","author":"Torbenson","year":"2002","journal-title":"Mod Pathol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/gut.17.7.551","article-title":"Gastric Morphology and Serum Gastrin Levels in Pernicious Anaemia","volume":"17","author":"Lewin","year":"1976","journal-title":"Gut"},{"key":"B26","article-title":"Active Autoimmune Gastritis Without Total Atrophy of the Glands","volume":"30","author":"Stolte","year":"1992","journal-title":"Z Gastroenterol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(96)80203-2","article-title":"The Histopathological Spectrum of Type A Gastritis","volume":"192","author":"Eidt","year":"1996","journal-title":"Pathol Res Pract"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000481","article-title":"Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for Appropriate Patient Evaluation","volume":"39","author":"Pittman","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.8178-21","article-title":"An Evaluation of Endoscopic Images From Over 15 Years Prior to the Diagnosis of Autoimmune Gastritis: A Report of Three Patients","author":"Ayaki","year":"2021","journal-title":"Intern Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2013-0261-RA","article-title":"The Clinical Significance of Duodenal Lymphocytosis With Normal Villus Architecture","volume":"137","author":"Hammer","year":"2013","journal-title":"Arch Pathol Lab Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-016-8841-7","article-title":"Pathophysiology and Laboratory Diagnosis of Pernicious Anemia","volume":"65","author":"Toh","year":"2017","journal-title":"Immunol Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.231","article-title":"Reassessment of Intrinsic Factor and Parietal Cell Autoantibodies in Atrophic Gastritis With Respect to Cobalamin Deficiency","volume":"104","author":"Lahner","year":"2009","journal-title":"Am J Gastroenterol"},{"key":"B33","article-title":"Evaluation of an ELISA for Detection of Antiparietal Cell Antibody","volume":"53","author":"Sugiu","year":"2006","journal-title":"Hepatogastroenterology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1053\/j.gastro.2021.06.078","article-title":"AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review","volume":"161","author":"Shah","year":"2021","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000238","article-title":"Low Pepsinogen I\/II Ratio and High Gastrin-17 Levels Typify Chronic Atrophic Autoimmune Gastritis Patients With Gastric Neuroendocrine Tumors","volume":"11","author":"Magris","year":"2020","journal-title":"Clin Transl Gastroenterol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.51.3.207","article-title":"Lymphocytic Gastritis and Coeliac Disease: Evidence of a Positive Association","volume":"51","author":"Feeley","year":"1998","journal-title":"J Clin Pathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.866167\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T07:22:35Z","timestamp":1651648955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.866167\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2022.866167"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.866167","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,4]]},"article-number":"866167"}}