{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:30:10Z","timestamp":1787927410716,"version":"build-2784847793"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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>Threatened abortion (TA), vaginal bleeding before 20 weeks in a viable pregnancy, affects 20-25% of early pregnancies. Its unpredictable nature is a major clinical challenge. Current diagnostics (\u03b2-hCG and ultrasound) are retrospective and fail to reveal the dynamic pathology. This review presents the \u201cDanger Signal\u201d Hypothesis, focusing on the \u03b2-hCG-TNF-\u03b1-T cell axis, to explain TA pathogenesis. The process involves three stages: 1) Initiation: Stressed trophoblasts secrete aberrantly glycosylated \u03b2-hCG, which acts as a DAMP. 2) Amplification: This DAMP triggers a TNF-\u03b1-dominated cytokine storm, reprogramming T cell metabolism to glycolysis and sustaining inflammation. 3) Execution: The inflammatory microenvironment induces trophoblast pyroptosis, creating a vicious cycle of damage. We synthesize evidence from glycobiology, immunometabolism, and cell death research to substantiate this model, explore its implications for the development of stage-specific biomarkers (such as \u03b2-hCG glycoforms and GSDMD-N fragments), and discuss precision therapeutic approaches (including the use of metformin for metabolic intervention and anti-TNF-\u03b1 agents for managing late-phase inflammation). This mechanistic framework aims to guide future research and improve clinical outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1749672","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:56:51Z","timestamp":1787925411000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The \u03b2-hCG-TNF-\u03b1-T cell axis in threatened abortion: unraveling the pathogenic cascade from aberrant glycosylation to inflammatory demise"],"prefix":"10.3389","volume":"17","author":[{"given":"Shimeng","family":"Wang","sequence":"first","affiliation":[{"name":"The 1st Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Guo","sequence":"additional","affiliation":[{"name":"Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingren","family":"Niu","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlu","family":"Ping","sequence":"additional","affiliation":[{"name":"The 1st Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Ren","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Qi","sequence":"additional","affiliation":[{"name":"The 2nd Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Feng","sequence":"additional","affiliation":[{"name":"The 1st Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","article-title":"First trimester bleeding: evaluation and management","volume":"99","author":"Hendriks","year":"2019","journal-title":"Am Fam Physician"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctcp.2021.101371","article-title":"Research on the medication rules of Chinese herbal formulas on treatment 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