Longitudinal proteomic profiling of the inflammatory response in dengue patients

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Abstract

Background The immunopathogenesis of dengue virus (DENV) infection remains incompletely under-stood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes in the inflammatory proteome in patients with an acute DENV infection. Methods Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10). Results We identified 203 upregulated and 39 downregulated proteins in acute versus convalescent plasma samples. The upregulated proteins had a strong representation of interferon (IFN) and IFN-inducible effector proteins, cytokines (e.g. IL-10, IL-33) and cytokine receptors, chemokines, pro-apoptotic proteins (e.g. granzymes) and endothelial markers. A number of differentially expressed proteins (DEPs) have not been reported in previous studies. Functional network analysis highlighted a central role for IFNγ, IL-10, IL-33 and chemokines. We identified different novel associations between inflammatory proteins and circulating con-centrations of the endothelial glycocalyx disruption surrogate marker syndecan-1. Conclusion: This unbiased proteome analysis provides a comprehensive insight in the inflammatory response in DENV infection and its association with glycocalyx disruption.

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Garishah, F. M., Boahen, C. K., Vadaq, N., Pramudo, S. G., Tunjungputri, R. N., Riswari, S. F., … de Mast, Q. (2023). Longitudinal proteomic profiling of the inflammatory response in dengue patients. PLoS Neglected Tropical Diseases, 17(1). https://doi.org/10.1371/journal.pntd.0011041

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