PLoS Neglected Tropical Diseases (Jan 2023)

Longitudinal proteomic profiling of the inflammatory response in dengue patients.

  • Fadel Muhammad Garishah,
  • Collins K Boahen,
  • Nadira Vadaq,
  • Setyo G Pramudo,
  • Rahajeng N Tunjungputri,
  • Silvita Fitri Riswari,
  • Ronald P van Rij,
  • Bachti Alisjahbana,
  • Muhammad Hussein Gasem,
  • André J A M van der Ven,
  • Quirijn de Mast

DOI
https://doi.org/10.1371/journal.pntd.0011041
Journal volume & issue
Vol. 17, no. 1
p. e0011041

Abstract

Read online

BackgroundThe immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. 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.MethodsUsing 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).ResultsWe 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 concentrations 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.