{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:49:08Z","timestamp":1782452948523,"version":"3.54.5"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Helicobacter pylori (H. pylori)<\/jats:italic>\n                      virulence factors, particularly CagA, determine pathogenic outcomes, yet their systemic serological impact remains poorly characterized. This study aimed to delineate systemic serological signatures associated with CagA-positive\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection, evaluate the novel biomarker CST4 as an exploratory pathophysiological indicator of host response to virulent infection, and develop predictive nomograms integrating host and bacterial factors for gastric diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study enrolled 565 participants who underwent bidirectional endoscopy with histopathological confirmation.\n                      <jats:italic>H. pylori<\/jats:italic>\n                      virulence-associated serotypes were identified using immunoblot analysis targeting CagA, VacA, UreA, and UreB proteins. Based on serological results, participants were categorized into three groups: Hp-negative, Hp I (positive for CagA and\/or VacA), and Hp II (positive only for UreA and\/or UreB). A comprehensive panel of serological parameters was assessed, including gastric function indicators (PG-I, PG-II, PG-I\/II ratio, and G-17), inflammatory markers, lipid profiles, coagulation indices, tumor markers, and serum CST4 levels. Multivariate logistic regression analysis was performed to determine independent predictors, which were subsequently used to develop predictive nomograms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CagA-positive infection, particularly the CagA\n                      <jats:sup>+<\/jats:sup>\n                      VacA\n                      <jats:sup>+<\/jats:sup>\n                      subtype, correlated with aggravated mucosal damage (elevated PG-II, reduced PG-I\/II ratio, both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Serum CST4 levels were significantly elevated in Hp I patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.032). The CST4-elevated group exhibited increased PG-I, PG-II, CA19-9, CA125, and D-dimer (all\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). CagA-positive infection was characterized by distinct systemic alterations: neutrophilia, elevated D-dimer and creatinine, shortened APTT, and reduced TC, HDL-C, and LDL-C (all\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). Younger age (OR\u00a0=\u00a00.976) and lower PG-I\/II ratio (OR\u00a0=\u00a00.890) independently predicted Hp I infection. Three nomograms integrating host and bacterial factors demonstrated robust discrimination for gastric polyps (AUC\u00a0=\u00a00.808), ulcers (AUC\u00a0=\u00a00.796), and cancer (AUC\u00a0=\u00a00.709), with favorable calibration and net clinical benefit by decision curve analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CagA-positive\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection induces a distinct systemic serological signature encompassing pro-inflammatory, pro-coagulant, hypolipidemic, and renal alterations, extending pathogenic impact beyond the gastric niche. Serum CST4 emerges as a promising exploratory pathophysiological indicator reflecting host systemic response to virulent infection, supporting its utility in screening and risk triage, while lesion-specific prediction is better achieved by nomograms integrating direct bacterial and host factors. The validated nomograms enable individualized risk stratification, supporting optimized clinical triage in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -infected populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1826407","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:43:57Z","timestamp":1782452637000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic serological signatures and novel biomarker CST4 link CagA-positive Helicobacter pylori to broad systemic alterations"],"prefix":"10.3389","volume":"16","author":[{"given":"Chonghe","family":"Xu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Capital Medical University","place":["Beijing, China"]},{"name":"Beijing Anzhen Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fourth Affiliated Hospital (Affiliated Chaohu Hospital) of Anhui Medical University","place":["Chaohu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fourth Affiliated Hospital (Affiliated Chaohu Hospital) of Anhui Medical University","place":["Chaohu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaosu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fourth Affiliated Hospital (Affiliated Chaohu Hospital) of Anhui Medical University","place":["Chaohu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fourth Affiliated Hospital (Affiliated Chaohu Hospital) of Anhui Medical University","place":["Chaohu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fourth Affiliated Hospital (Affiliated Chaohu Hospital) of Anhui Medical University","place":["Chaohu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","first-page":"299","article-title":"An evaluation of laboratory tests for COVID-19 infection in patients residing in the Baghdad - Iraq","volume":"23","author":"Al-Jindeel","year":"2023","journal-title":"Int. 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