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

作者：Dang My Nhi; Nguyen Tien Huy^*; Ohyama Kaname; Kimura Daisuke; Nguyen Thi Phuong Lan; Uchida Leo; Nguyen Van Thuong; Cao Thi My Nhon; Phuc Le Hong; Nguyen Thi Mai; Mizukami Shusaku; Lam Quoc Bao; Nguyen Ngoc Doan; Nguyen Van Thanh Binh; Luong Chan Quang; Karbwang Juntra; Yui Katsuyuki; Morita Kouichi; Vu Thi Que Huong; Hirayama Kenji^*

来源：PLoS Neglected Tropical Diseases, 2016, 10(2): e0004435.

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.

• 出版日期2016-2