A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children e0004435

• Published in: PLoS neglected tropical diseases Vol. 10; no. 2
• Main Authors: Nhi, Dang My, Huy, Nguyen Tien, Ohyama, Kaname, Kimura, Daisuke, Lan, Nguyen ThiPhuong, Uchida, Leo, Thuong, Nguyen Van, Nhon, Cao ThiMy, Phuc, Le Hong, Mai, Nguyen Thi, Mizukami, Shusaku, Bao, Lam Quoc, Doan, Nguyen Ngoc, Binh, Nguyen VanThanh, Quang, Luong Chan, Karbwang, Juntra, Yui, Katsuyuki, Morita, Kouichi, Huong, Vu ThiQue, Hirayama, Kenji
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.02.2016
• Subjects: Biomarkers; Disease; Heparan sulfate; Hospitalization; Hospitals; Infections; Medical research; Medicine; Mortality; Pediatrics; Plasma; Proteins; Tropical diseases
• ISSN: 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0004435

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.