Quantitative Comparative Proteomics Reveal Biomarkers for Dengue Disease Severity

Area of Science:

• Biochemistry
• Molecular Biology
• Clinical Medicine

Background:

• Dengue fever (DF) can progress to dengue hemorrhagic fever (DHF), a severe form with higher mortality.
• Clinical presentation and causative agents are similar in DF and DHF, necessitating distinct biomarkers for prediction.
• Early identification of individuals at risk for DHF is crucial for timely intervention.

Purpose of the Study:

• To identify differential protein expression in dengue fever (DF) patients who later develop dengue hemorrhagic fever (DHF).
• To discover novel molecular biomarkers for predicting DHF development from DF.
• To validate proteomic findings using independent molecular techniques.

Main Methods:

• Quantitative proteomics using TMT-label based methodology on plasma samples.
• Analysis of differentially expressed proteins and enrichment in biological pathways.
• Validation of key protein and gene expression using RT-PCR and ELISA in a cohort of 54 individuals.

Main Results:

• 441 proteins were identified as differentially expressed between DF and DHF patients compared to healthy controls.
• Proteins involved in proteasome pathway, amino acid metabolism, and biosynthesis were significantly altered.
• Specific proteins (e.g., PLAT, LAMB2, F9) were upregulated in DF patients who progressed to DHF, while others (FGL1, MFAP4, GLUL, VCAM1) were elevated in both DF and DHF.

Conclusions:

• Several identified proteins, including PLAT, LAMB2, F9, VCAM1, FGL1, MFAP4, and GLUL, show potential as predictive biomarkers for DHF.
• These biomarkers could facilitate precision medicine approaches for early DHF risk stratification in DF patients.
• The findings open avenues for developing diagnostic tools to distinguish DF from DHF and predict disease severity.