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A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children
Dang My Nhi1, Nguyen Tien Huy2, Kaname Ohyama3,4
1Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Insights
Early detection of severe dengue with severe plasma leakage (SD-SPL) is crucial. Researchers identified specific plasma proteins, including antithrombin III, that can predict SD-SPL before shock, aiding timely clinical management.
Area of Science:
- Biochemistry
- Clinical Diagnostics
- Dengue Pathogenesis
Background:
- Severe dengue with severe plasma leakage (SD-SPL) is the most common severe dengue manifestation.
- Early predictive plasma biomarkers are needed for timely clinical management in primary care settings to prevent mortality.
Purpose of the Study:
- To identify specific plasma proteins that are differentially expressed in patients with SD-SPL compared to those with dengue with warning signs (DWS).
- To evaluate the potential of these proteins as early diagnostic markers for SD-SPL.
Main Methods:
- A hospital-based longitudinal study involving 63 pediatric dengue patients.
- Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to analyze plasma proteomes from SD-SPL and DWS groups.
- Validation of identified protein markers was performed.
Main Results:
- Nineteen plasma proteins showed significant concentration differences between SD-SPL and DWS groups (p<0.05).
- Five proteins were over-expressed and fourteen were under-expressed in SD-SPL.
- Angiotensinogen and antithrombin III levels were significantly increased in early-stage SD-SPL plasma; antithrombin III demonstrated predictive accuracy for SD-SPL before shock.
Conclusions:
- Identified proteins, including antithrombin III, show promise as candidate predictive markers for early diagnosis of SD-SPL.
- Timely clinical management can be facilitated by these potential biomarkers.
- Further studies are required to validate these findings in larger cohorts.
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.
