{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:25:23Z","timestamp":1775024723219,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011645","name":"Kaohsiung Medical University Chung-Ho Memorial Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dengue is a global health threat, with severe cases causing significant complications. Cytokines have been proposed as potential indicators of disease severity; however, the short plasma half-life and pre-analytical instability of free-form cytokines limit their clinical applicability. Exosome-encapsulated cytokines are protected by a lipid bilayer and may provide a more stable and integrated representation of host immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, we analyzed single time-point plasma samples collected from patients during clinical evaluation between July and December 2023, with most samples obtained during the acute phase (within 7 days post-symptom onset). Plasma exosomes were isolated from patients with mild dengue, dengue with warning signs (DFWS), severe dengue (SD), other febrile illnesses, and healthy controls (HCs). Exosome-associated cytokines were quantified using a multiplex panel assessing 15 cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across the five study groups, significant differences in plasma exosome cytokine levels were observed for interleukin (IL)-1\u03b2, IL-6, IL-10, IL-12, interferon-\u03b3 (IFN-\u03b3), and tumor necrosis factor (TNF)-\u03b1 (all p &amp;lt; 0.05). Post-hoc analyses further demonstrated that IL-6, IL-10, and TNF-\u03b1 levels were significantly higher in both the DFWS and SD groups compared with HCs (all p &amp;lt; 0.01). In a subsequent analysis comparing mild dengue with the combined DFWS\/SD group, significantly higher exosomal levels of IL-1\u03b2, IL-5, IL-10, IL-12, IL-13, and TNF-\u03b1 were observed in the DFWS\/SD group (all p &amp;lt; 0.05). Receiver operating characteristic (ROC) analysis showed that IL-1\u03b2, IL-10, and TNF-\u03b1 moderately discriminated mild from severe cases, with area under the curve (AUC) values of approximately 0.7. An \u201call-positive\u201d panel (TNF-\u03b1, IL-10, and IL-1\u03b2) achieved 84% sensitivity and 67.5% specificity for identifying DFWS\/SD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that combined exosomal cytokine profiling may aid in disease severity stratification. However, given the cross-sectional design and moderate discriminatory performance, larger prospective studies are needed to validate its clinical applicability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1779100","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:25:22Z","timestamp":1775017522000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Profiling of plasma exosome cytokines as biomarkers of severe dengue"],"prefix":"10.3389","volume":"17","author":[{"given":"Chien-Tai","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Neurology, Taipei Medical University-Shuang Ho Hospital","place":["New Taipei, Taiwan"]},{"name":"Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Teh","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology","place":["Tainan, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]},{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University","place":["Kaohsiung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes","place":["Miaoli City, Taiwan"]},{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Miaoli City, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Yi","family":"Tsai","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping-Chang","family":"Lin","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao-Chen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jih-Jin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]},{"name":"School of Medicine, College of Medicine, Kaohsiung Medical University","place":["Kaohsiung, Taiwan"]},{"name":"Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital","place":["Kaohsiung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100712","article-title":"Global, regional, and national dengue burden from 1990 to 2017: A systematic analysis based on the global burden of disease study 2017","volume":"32","author":"Zeng","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B3","article-title":"WHO guidelines approved 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