title: Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection.
abstract: BACKGROUND
  Dengue virus (DENV) is described as the most prevalent arbovirus, infecting at least 50 million people worldwide. During infection, an intricate network of cytokines, a group of substances closely related to disease severity, is released. Recently, it was observed that both DENV-infected epithelial cells undergoing necrosis and dendritic cells (DCs) are able to release a non-classical pro-inflammatory cytokine called high mobility group box 1 (HMGB1).
  
  
  OBJECTIVE
  The aim of this study was to evaluate whether HMGB1 levels were altered in DENV-infected patients' sera and whether this augment correlated with disease pathogenesis.
  
  
  METHODS
  Samples from DENV-infected patients were collected from different days after the onset of symptoms and from patients experiencing primary or secondary infection. The circulating HMGB1 concentration was measured in healthy blood donors as well as in donors with primary and secondary cases of DENV infection by a quantitative capture ELISA assay.
  
  
  RESULTS
  We observed that the HMGB1 concentration in DENV-infected patients was significantly higher than in healthy patients. HMGB1 levels reached the highest concentration in the first day after the onset of symptoms and decreased throughout the course of the infection. Moreover, we observed that the HMGB1 concentration was augmented during secondary infection as well.
  
  
  CONCLUSIONS
  We hypothesize that HMGB1 levels correlate with disease pathogenesis, specifically with the clinical symptoms and secondary infection, implicating a pro-inflammatory cytokine role for HMGB1 in DENV infection. This is the first report assessing the circulating levels of HMGB1 during DENV infection.
authors.affiliation: Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Allonso
authors.forename: Fabricio S
authors.initials: FS
authors.lastname: Belgrano
authors.forename: Naifi
authors.initials: N
authors.lastname: Calzada
authors.forename: Maria G
authors.initials: MG
authors.lastname: Guzmán
authors.forename: Susana
authors.initials: S
authors.lastname: Vázquez
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Mohana-Borges
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003715:Dengue / Q000175:diagnosis* / Q000473:pathology*; D003716:Dengue Virus; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D044967:Serum / Q000737:chemistry*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein