Review 2: "Proteomics Analysis of Peripheral Blood Monocytes from Patients in Early Dengue Infection Reveals Potential Markers of Subsequent Fluid Leakage"

Sujatha Sunil

doi:doi:10.1162/2e3983f5.e36b15cd

Proteomics analysis of peripheral blood monocytes from patients in early dengue infection reveals potential markers of subsequent fluid leakage

by Nilanka Perera, Abhinav Kumar, Bevin Gangadharan, Diyanath Ranasinghe, Ananda Wijewickrama, Gathsaurie Neelika Malavige, Joanna L. Miller, and Nicole Zitzmann

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Published on Mar 26, 2024
www.medrxiv.org

Description

Abstract Infections caused by dengue virus (DENV) cause significant morbidity and mortality worldwide. The majority of patients have a mild course of dengue fever (DF) disease, however a proportion of infected individuals develop much more severe dengue haemorrhagic fever (DHF) resulting in circulatory collapse and multiorgan failure due to increased vascular permeability. Early detection of individuals likely to develop severe disease could lead to improved outcomes for patients, and help use healthcare resources more efficiently. At present there are no reliable markers during the earlier stages of infection that indicate which patients will go on to develop DHF. Our study was aimed at identifying proteins that are differentially regulated early during disease in peripheral blood monocytes (PBMC) of patients who subsequently develop DHF. Such proteins may also point at cellular pathways implicated in developing vascular leakage. PBMC were isolated from patients with a confirmed dengue infection, lysed and subjected to tandem mass tag mass spectrometry. One hundred and sixty proteins were differentially expressed in DENV-infected samples compared to healthy controls. These were mainly involved in type I interferon signaling, cytokine response, phagocytosis, haemostasis and cell adhesion. PBMC from DHF patients differentially expressed 90 proteins compared to individuals with DF; these were involved in down-regulation of platelet activation and aggregation, cell adhesion and cytoskeleton arrangement pathways. Proteins involved in oxidative stress and p38 MAPK signaling were upregulated in DHF samples during early infection compared to DF samples. The proteins reported here that are differentially regulated in PBMC early during infection could potentially serve as biomarkers to identify patients at risk of developing DHF at an early disease stage. This study also provides important observations on pathways implicated in severe DENV infection.

RR:C19 Evidence Scale rating by reviewer:

Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: The authors have conducted a comprehensive analysis of proteins altered in peripheral blood monocytes from dengue infection patients during early phases to see the markers of fluid leakage. The study is quite interesting and provides early protein markers during dengue haemorrhagic fever for providing better healthcare in critical patients. However, few minor concerns need to be addressed. These are as follows:

The authors can suggest the names of the differentially regulated proteins as marker for fluid leakage if possible. This is important as the present study delineates the proteins marker for the same as compared to the previous studies.
It would be very convincing if the authors provide the validation of top differentially regulated proteins via qRT-PCR or western blotting.
The authors could conduct the cell line-based inhibitor study to confirm the pathways downregulted in DHF patients especially candidate protein for platelet activation and aggregation, cell adhesion. If not please provide the justification as limitation in discussion.

Review 2: "Proteomics Analysis of Peripheral Blood Monocytes from Patients in Early Dengue Infection Reveals Potential Markers of Subsequent Fluid Leakage"

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