A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

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. METHODOLOGY:Among 63 confirmed dengue pediatric patients recruit...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Dang My Nhi, Nguyen Tien Huy, Kaname Ohyama, Daisuke Kimura, Nguyen Thi Phuong Lan, Leo Uchida, Nguyen Van Thuong, Cao Thi My Nhon, Le Hong Phuc, Nguyen Thi Mai, Shusaku Mizukami, Lam Quoc Bao, Nguyen Ngoc Doan, Nguyen Van Thanh Binh, Luong Chan Quang, Juntra Karbwang, Katsuyuki Yui, Kouichi Morita, Vu Thi Que Huong, Kenji Hirayama
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2016
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Online Access:https://doi.org/10.1371/journal.pntd.0004435
https://doaj.org/article/6ce086f8fcc74e3a9da3685dc2991e3c
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Summary: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. METHODOLOGY: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. PRINCIPAL FINDINGS: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. CONCLUSION: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.

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