{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:54:36Z","timestamp":1785876876809,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Centers for Disease Control and Prevention","award":["5 U01IP001106"],"award-info":[{"award-number":["5 U01IP001106"]}]},{"name":"United States Centers for Disease Control and Prevention","award":["Ym2023016"],"award-info":[{"award-number":["Ym2023016"]}]},{"name":"Jiangsu Province Preventive Medicine Research Project","award":["5 U01IP001106"],"award-info":[{"award-number":["5 U01IP001106"]}]},{"name":"Jiangsu Province Preventive Medicine Research Project","award":["Ym2023016"],"award-info":[{"award-number":["Ym2023016"]}]},{"name":"Project of the Suzhou Science and Technology Bureau","award":["5 U01IP001106"],"award-info":[{"award-number":["5 U01IP001106"]}]},{"name":"Project of the Suzhou Science and Technology Bureau","award":["Ym2023016"],"award-info":[{"award-number":["Ym2023016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Seasonal influenza infection poses substantial risks to pregnant women, yet the immunological mechanisms underlying their heightened disease susceptibility remain incompletely characterized. Methods: This study employed multiparametric immunophenotyping and metabolic profiling to investigate cellular immunity, cytokine dynamics, and serum biomarkers in pregnant women infected with H3N2 across gestational stages. Through integrated flow cytometric analysis of peripheral blood mononuclear cells (PBMCs), multiple cytokine quantification, and LC-MS-based serum metabolomics, we compared immunological parameters, serum cytokines, and metabolites across trimesters in pregnant women infected and not infected with H3N2. Results: The results revealed reduced CD4+\/CD8+ T cell ratios, a diminished CD27+ memory B cell population in pregnant women infected with H3N2, and elevated NK cells and Th2-skewed cytokines (IL-4, IL-6, IL-10) in severe influenza cases. Metabolomic profiling identified the dysregulation of the tryptophan\u2013kynurenine (Trp\u2013Kyn) pathway, with a 15-fold increase in the Kyn\/Trp ratio in severe influenza compared to a normal pregnancy as a potential biomarker. Conclusions: These results elucidate synergistic pathophysiological axes-immune dysregulation and tryptophan metabolism alteration that potentially drive adverse outcomes. The identified biomarker panel (CD4\/CD8 ratio, IL-6, Kyn\/Trp ratio) shows potential clinical promise for early risk stratification in high-risk pregnancies with influenza infection.<\/jats:p>","DOI":"10.3390\/diseases13060182","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T08:18:43Z","timestamp":1749543523000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune Response and Serum Biomarker Screening in Pregnant Women with Influenza A Virus Infection: Insight into Susceptibility and Disease Severity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2028-5199","authenticated-orcid":false,"given":"Suping","family":"Zhang","sequence":"first","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"},{"name":"School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarun","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7614-0251","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"},{"name":"School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3318-1055","authenticated-orcid":false,"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Sun","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"},{"name":"School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-8786","authenticated-orcid":false,"given":"Wanting","family":"Hong","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"},{"name":"School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-3346","authenticated-orcid":false,"given":"Likai","family":"Qi","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zang","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Institue of Respiratory Diseases, Soochow University, Suzhou 215006, China"},{"name":"Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-6568","authenticated-orcid":false,"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8385-5377","authenticated-orcid":false,"given":"Haibing","family":"Yang","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2868-741X","authenticated-orcid":false,"given":"Liling","family":"Chen","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou 215131, China"},{"name":"School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: A modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s12276-021-00603-0","article-title":"The evolution and future of influenza pandemic preparedness","volume":"53","author":"Harrington","year":"2021","journal-title":"Exp. 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