title: Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection.
abstract: BACKGROUND
  Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases.
  
  
  OBJECTIVE
  The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection.
  
  
  METHODS
  A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined using commercially available ELISAs.
  
  
  RESULTS
  Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR-2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage.
  
  
  CONCLUSIONS
  Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.
authors.affiliation: Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Cornelia A M
authors.initials: CA
authors.lastname: van de Weg
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Cláudio S
authors.initials: CS
authors.lastname: Pannuti
authors.affiliation: Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: van den Ham
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil; Department of Infectious Diseases, Hospital Ana Costa, Rua Pedro Américo 60, Campo Grande 11075-400, Santos, Brazil.
authors.forename: Evaldo S A
authors.initials: ES
authors.lastname: de Araújo
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Lucy S V
authors.initials: LS
authors.lastname: Boas
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Alvina C
authors.initials: AC
authors.lastname: Felix
authors.affiliation: Hospital Albert Einstein, Av. Albert Einstein 627, CEP 05652-000 São Paulo, Brazil.
authors.forename: Karina I
authors.initials: KI
authors.lastname: Carvalho
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Levi
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Romano
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Cristiane C
authors.initials: CC
authors.lastname: Centrone
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Celia L de Lima
authors.initials: CL
authors.lastname: Rodrigues
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, Brazil.
authors.forename: Expedito
authors.initials: E
authors.lastname: Luna
authors.affiliation: Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Eric C M
authors.initials: EC
authors.lastname: van Gorp
authors.affiliation: Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Disciplina de Imunologia Clínica e Alergia (LIM-60), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 155, CEP 05403-000 São Paulo, Brazil.
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.affiliation: Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: b.martina@erasmusmc.nl.
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
mesh_terms: D000293:Adolescent; D000328:Adult; D042702:Angiopoietin-2 / Q000097:blood*; D000914:Antibodies, Viral / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D002199:Capillary Permeability / Q000502:physiology*; D016022:Case-Control Studies; D002648:Child; D003716:Dengue Virus / Q000472:pathogenicity; D042783:Endothelial Cells / Q000473:pathology / Q000821:virology; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D011859:Radiography; D019595:Severe Dengue / Q000097:blood* / Q000000981:diagnostic imaging / Q000821:virology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D055815:Young Adult
chemical_list: D042702:Angiopoietin-2; D000914:Antibodies, Viral; D015415:Biomarkers; D019332:Endothelin-1; D007074:Immunoglobulin G; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D020778:Matrix Metalloproteinase 2
keywords: Angiopoietin-2; Dengue virus; Plasma leakage; Soluble VEGFR-2; Vascular permeability