Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

Abstract

BackgroundWe report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples.Methodology/Principal FindingsThe study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels.Conclusions/SignificanceSome of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection.

The Early Whole-Blood Transcriptional Signature of Dengue Virus and Features Associated with Progression to Dengue Shock Syndrome in Vietnamese Children and Young Adults

“…The timing of sample collection is clearly a major factor in the transcriptional signature, with samples collected during the febrile phase having characteristic antiviral profiles, e.g., with interferon-stimulated genes being highly prominent (11,26,36), while those collected during the afebrile stage having predominantly metabolic profiled (26,36). Studies of peripheral blood mononuclear cells (PBMC) (i.e., minus the neutrophil population) have also been described (30,40). In short, however, all previous microarray studies of the dengue host response have used relatively small amounts of samples collected at heterogenous time points and rarely included patients with DSS, the commonest life-threatening complication in children.…”

1 H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients

“…Genomics (8,9) and proteomics (10)(11)(12) have been used by different research groups in an attempt to identify early markers of dengue disease and/or its severity. More recently, metabolomics, the study of low-molecular-weight metabolites of physiological relevance, has proved an important tool for studying the changes in host metabolism during the course of viral infections (13)(14)(15)(16)(17).…”

Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood

“…However, a robust test incorporating a large panel of molecules will likely be required for the accurate prognosis and differential diagnosis of CM. Interestingly, a recent study conducted on a dengue cohort in Brazil demonstrated that microarray analysis of peripheral blood mononuclear cells could be used to design gene expression signatures that accurately predict which cases of acute febrile dengue progress into dengue hemorrhagic fever (28).…”