title: Severity of Plasma Leakage Is Associated With High Levels of Interferon γ-Inducible Protein 10, Hepatocyte Growth Factor, Matrix Metalloproteinase 2 (MMP-2), and MMP-9 During Dengue Virus Infection.
abstract: BACKGROUND
  Dengue virus infection typically causes mild dengue fever, but, in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occur. The pathophysiological hallmark of DHF and DSS is plasma leakage that leads to enhanced vascular permeability, likely due to a cytokine storm.
  
  
  METHODS
  Ninety patients with dengue during 2010-2012 in Singapore were prospectively recruited and stratified according to their disease phase, primary and secondary infection status, and disease severity, measured by plasma leakage. Clinical parameters were recorded throughout the disease progression. The levels of various immune mediators were quantified using comprehensive multiplex microbead-based immunoassays for 46 immune mediators.
  
  
  RESULTS
  Associations between clinical parameters and immune mediators were analyzed using various statistical methods. Potential immune markers, including interleukin 1 receptor antagonist, interferon γ-inducible protein 10, hepatocyte growth factor, soluble p75 tumor necrosis factor α receptor, vascular cell adhesion molecule 1, and matrix metalloproteinase 2, were significantly associated with significant plasma leakage. Secondary dengue virus infections were also shown to influence disease outcome in terms of disease severity.
  
  
  CONCLUSIONS
  This study identified several key markers for exacerbated dengue pathogenesis, notably plasma leakage. This will allow a better understanding of the molecular mechanisms of DHF and DSS in patients with dengue.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Her
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Yiu-Wing
authors.initials: YW
authors.lastname: Kam
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Gan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital.
authors.forename: Tun-Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Jeslin J L
authors.initials: JJ
authors.lastname: Tan
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital.|Saw Swee Hock School of Public Health, National University of Singapore.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research.|Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D000328:Adult; D002199:Capillary Permeability; D054357:Chemokine CXCL10 / Q000097:blood*; D060085:Coinfection / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003715:Dengue / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000276:immunology; D065288:Serogroup; D019595:Severe Dengue / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D012846:Singapore; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000276:immunology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; C066855:HGF protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; D017228:Hepatocyte Growth Factor; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: cytokines; dengue virus; plasma leakage