ArticleFrontiers in immunology2026
Profiling of plasma exosome cytokines as biomarkers of severe dengue.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: 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. Methods: 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. Results: Across the five study groups, significant differences in plasma exosome cytokine levels were observed for interleukin (IL)-1β, IL-6, IL-10, IL-12, interferon-γ (IFN-γ), and tumor necrosis factor (TNF)-α (all p < 0.05). Post-hoc analyses further demonstrated that IL-6, IL-10, and TNF-α levels were significantly higher in both the DFWS and SD groups compared with HCs (all p < 0.01). In a subsequent analysis comparing mild dengue with the combined DFWS/SD group, significantly higher exosomal levels of IL-1β, IL-5, IL-10, IL-12, IL-13, and TNF-α were observed in the DFWS/SD group (all p < 0.05). Receiver operating characteristic (ROC) analysis showed that IL-1β, IL-10, and TNF-α moderately discriminated mild from severe cases, with area under the curve (AUC) values of approximately 0.7. An "all-positive" panel (TNF-α, IL-10, and IL-1β) achieved 84% sensitivity and 67.5% specificity for identifying DFWS/SD. Conclusion: 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.
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