title: A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.
abstract: BACKGROUND
  Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.
  
  
  METHODS
  Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.
  
  
  RESULTS
  Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.
  
  
  CONCLUSIONS
  Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Dang My
authors.initials: DM
authors.lastname: Nhi
authors.affiliation: Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.affiliation: Department of Environmental and Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.|Nagasaki University Research Centre for Genomic Instability and Carcinogenesis (NRGIC), Nagasaki, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Ohyama
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kimura
authors.affiliation: Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thi Phuong
authors.initials: NT
authors.lastname: Lan
authors.affiliation: Department of Virology, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Leo
authors.initials: L
authors.lastname: Uchida
authors.affiliation: Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Thuong
authors.affiliation: Nguyen Dinh Chieu Hospital, Ben Tre Province, Vietnam.
authors.forename: Cao Thi My
authors.initials: CT
authors.lastname: Nhon
authors.affiliation: Nguyen Dinh Chieu Hospital, Ben Tre Province, Vietnam.
authors.forename: Le Hong
authors.initials: le H
authors.lastname: Phuc
authors.affiliation: Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Mai
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Mizukami
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Lam Quoc
authors.initials: LQ
authors.lastname: Bao
authors.affiliation: Nguyen Dinh Chieu Hospital, Ben Tre Province, Vietnam.
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Doan
authors.affiliation: Nguyen Dinh Chieu Hospital, Ben Tre Province, Vietnam.
authors.forename: Nguyen Van Thanh
authors.initials: NV
authors.lastname: Binh
authors.affiliation: Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam.
authors.forename: Luong Chan
authors.initials: LC
authors.lastname: Quang
authors.affiliation: Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Juntra
authors.initials: J
authors.lastname: Karbwang
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Yui
authors.affiliation: Department of Virology, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam.
authors.forename: Vu Thi Que
authors.initials: VT
authors.lastname: Huong
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D040901:Proteomics / Q000379:methods*; D019595:Severe Dengue / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers