{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:22:33Z","timestamp":1787638953271,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Autoimmune gastritis (AIG) arises from a T-cell\u2013mediated immune attack on the gastric parietal cell and carries a dual neoplastic risk: gastric adenocarcinoma through spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia, and type-1 gastric neuroendocrine tumour (NET) through hypergastrinaemia-driven enterochromaffin-like (ECL) cell hyperplasia. This \u201cone origin, two fates\u201d framework is conceptually established but has never been given a molecular trajectory from an AIG origin, and molecular data for the neuroendocrine endpoint are essentially absent. We integrated public single-cell transcriptomes of the human AIG corpus (GSE271866; three samples, 14,323 cells) and of a histologically staged premalignant cascade (GSE134520; 44,012 cells) with a cross-sectional cohort of approximately 203 AIG patients, treating the two axes asymmetrically: the adenocarcinoma axis was reconstructed at the molecular level, whereas the neuroendocrine axis was clinically and literature anchored. The AIG corpus showed near-absent parietal cells (0.45%) with extensive SPEM (18.6%) and intestinal metaplasia (16.3%). Cascade pseudotime increased monotonically with histological stage (Spearman\u2019s\n                    <jats:italic>\u03c1<\/jats:italic>\n                    =\u00a00.496; unchanged on the unbridged graph) and defined a gastric-to-intestinal progression signature that, transferred to the AIG corpus, tracked the AIG-intrinsic pseudotime (\n                    <jats:italic>\u03c1<\/jats:italic>\n                    =\u00a00.673). Most AIG metaplastic cells were projected to the strong-metaplasia stage (90.9%; bootstrap 95% CI 84\u201398%;\n                    <jats:italic>n<\/jats:italic>\n                    =\u00a055), a suggestive rather than definitive placement that is nonetheless consistent with AIG occupying the atrophy-to-metaplasia segment of the adenocarcinoma axis. In the cohort, hypergastrinaemia scaled with corpus atrophy (gastrin-17 versus pepsinogen I\/II ratio\n                    <jats:italic>\u03c1<\/jats:italic>\n                    = \u22120.413,\n                    <jats:italic>p<\/jats:italic>\n                    =\u00a09.9 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ), and single-cell analysis confirmed a gastrin-responsive ECL population (\n                    <jats:italic>HDC<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    93%,\n                    <jats:italic>CCKBR<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    76%) whose neuroendocrine programme was orthogonal to the intestinal programme of the adenocarcinoma arm. Because AIG is a prototypic autoimmune disease, we frame how the autoimmune infiltrate steers each fate as the central open immunological question. AIG thus enters the metaplasia-to-cancer axis from a corpus, parietal-cell-loss origin and diverges, through a serum-gastrin\u2013ECL bridge, towards the neuroendocrine fate; we provide an interpretable progression signature and a severity-anchored, hypothesis-generating framework\u2014not an outcome predictor, since the cohort is cross-sectional with essentially no neoplastic endpoints\u2014and report the molecular data gap for the neuroendocrine endpoint as a field-level priority.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1899802","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:35:07Z","timestamp":1787636107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoimmune gastritis diverges from a shared corpus origin: molecular reconstruction of the adenocarcinoma axis and clinical anchoring of the neuroendocrine axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingna","family":"Tao","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghan","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine Oncology, Hangzhou Cancer Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Li","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05101.x","article-title":"Autoimmune 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