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

• Published in: PLoS neglected tropical diseases Vol. 10; no. 2; p. e0004435
• Main Authors: Nhi, Dang My, Huy, Nguyen Tien, Ohyama, Kaname, Kimura, Daisuke, Lan, Nguyen Thi Phuong, Uchida, Leo, Thuong, Nguyen Van, Nhon, Cao Thi My, Phuc, Le Hong, Mai, Nguyen Thi, Mizukami, Shusaku, Bao, Lam Quoc, Doan, Nguyen Ngoc, Binh, Nguyen Van Thanh, Quang, Luong Chan, Karbwang, Juntra, Yui, Katsuyuki, Morita, Kouichi, Huong, Vu Thi Que, Hirayama, Kenji
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.02.2016; Public Library of Science (PLoS)
• Subjects: Adolescent; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood proteins; Child; Child, Preschool; Children; Dengue fever; Diagnosis; Disease; Female; Health aspects; Heparan sulfate; Hospitalization; Hospitals; Humans; Infections; Longitudinal Studies; Male; Medical research; Medicine; Medicine and Health Sciences; Mortality; Pediatrics; Plasma; Prevention; Proteins; Proteomics - methods; Severe Dengue - blood; Severe Dengue - diagnosis
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0004435

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. 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. 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. 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.