Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

Poole-Smith, B. Katherine; Gilbert, Alexa; Gonzalez, A. Lorenzo; Beltrán, Manuela; Tomashek, Kay M.; Ward, Brian J.; Hunsperger, Elizabeth; Ndao, Momar

doi:10.4269/ajtmh.14-0193

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…HPX levels may help determine the severity of the illness, discriminate between dengue hemorrhagic fever (DHF) and uncomplicated dengue fever (DF), which would aid in diagnosis and treatment; and fibronectin, HPX and transferrin were found to be significantly decreased in DHF (Kumar et al, 2012 ). In other studies, HPX and vitronectin were increased in DF and DHF (Poole-Smith et al, 2014 ). Although by no means proven [see references in (Poole-Smith et al, 2014 ) on data from other human and swine studies], HPX together with other biomarkers such as Hp, may prove useful as a supplement in certain stages of hemorrhagic shock and even, potentially in the progression of Ebola in patients, especially those that progress to hemorrhage .…”

Section: Heme Toxicity and Hemopexin Deficiency Statesmentioning

confidence: 62%

“…In other studies, HPX and vitronectin were increased in DF and DHF (Poole-Smith et al, 2014 ). Although by no means proven [see references in (Poole-Smith et al, 2014 ) on data from other human and swine studies], HPX together with other biomarkers such as Hp, may prove useful as a supplement in certain stages of hemorrhagic shock and even, potentially in the progression of Ebola in patients, especially those that progress to hemorrhage .…”

Section: Heme Toxicity and Hemopexin Deficiency Statesmentioning

confidence: 62%

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Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

2015

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The goal here is to describe our current understanding of heme metabolism and the deleterious effects of “free” heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of hemopexin (HPX). Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease (SCD), and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp) is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular (IVH) inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as SCD, sepsis, hemolytic-uremic syndrome, and conditions involving IVH and extravascular hemolysis (EVH), such as that generated by extracorporeal circulation during cardiopulmonary bypass (CPB) and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX, and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e., “replenishment”) therapies for patients with heme toxicity due to HPX depletion.

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Section: Heme Toxicity and Hemopexin Deficiency Statesmentioning

confidence: 62%

Section: Heme Toxicity and Hemopexin Deficiency Statesmentioning

confidence: 62%

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

2015

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“…It was surprising that PCA revealed little clustering of Mexican samples by dengue diagnosis group in contrast to the Nicaraguan samples ( Fig 2A and 2B ). Many factors have been demonstrated to condition dengue disease severity, including infecting DENV serotype and genotype and primary or secondary infections [ 24 , 60 , 61 ], which could have confounded the analyses. The Mexican patients were infected with either DENV-1 or DENV-2; only DENV-2 was detected in Nicaraguan patients.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

et al. 2016

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BackgroundEpidemic dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and clinical care of dengue patients throughout the tropical and subtropical world. The ability to predict severe dengue disease outcomes (DHF/DSS) using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management. Advances in the field of metabolomics and analytic software provide new opportunities to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that differentiate dengue disease outcomes.Methodology/Principal FindingsExploratory metabolomic studies were conducted to characterize the serum metabolome of patients who experienced different dengue disease outcomes. Serum samples from dengue patients from Nicaragua and Mexico were retrospectively obtained, and hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) identified small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. In the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes. In the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS). Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. Differential perturbation of the serum metabolome was demonstrated following infection with different DENV serotypes and following primary and secondary DENV infections.Conclusions/SignificanceThese results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum specimens that are associated with distinct DENV infections and disease outcomes. The differentiating metabolites also provide insights into metabolic pathways and pathogenic and immunologic mechanisms associated with dengue disease severity.

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“…Interestingly, MS allows deciphering virus structural variability (as previously exemplified for bacteriophages) and evolution, through proteotyping and sequence analysis . An alternative may rely on indirect markers of exposition that could be established by specific proteomic approaches aiming at measuring changes in host proteins upon viral infection …”

Section: Emerging and Other Specific Approaches In The Environmental mentioning

confidence: 99%

“…[113,[121][122][123][124][125] An alternative may rely on indirect markers of exposition that could be established by specific proteomic approaches aiming at measuring changes in host proteins upon viral infection. [126][127][128][129]…”

Section: Analysis Of Virusesmentioning

confidence: 99%

Mass spectrometry for the detection of bioterrorism agents: from environmental to clinical applications

Duriez¹,

Armengaud

Fenaille

et al. 2016

J. Mass Spectrom.

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In the current context of international conflicts and localized terrorist actions, there is unfortunately a permanent threat of attacks with unconventional warfare agents. Among these, biological agents such as toxins, microorganisms, and viruses deserve particular attention owing to their ease of production and dissemination. Mass spectrometry (MS)-based techniques for the detection and quantification of biological agents have a decisive role to play for countermeasures in a scenario of biological attacks. The application of MS to every field of both organic and macromolecular species has in recent years been revolutionized by the development of soft ionization techniques (MALDI and ESI), and by the continuous development of MS technologies (high resolution, accurate mass HR/AM instruments, novel analyzers, hybrid configurations). New possibilities have emerged for exquisite specific and sensitive detection of biological warfare agents. MS-based strategies for clinical application can now address a wide range of analytical questions mainly including issues related to the complexity of biological samples and their available volume. Multiplexed toxin detection, discovery of new markers through omics approaches, and identification of untargeted microbiological or of novel molecular targets are examples of applications. In this paper, we will present these technological advances along with the novel perspectives offered by omics approaches to clinical detection and follow-up.

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Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

Cited by 9 publications

References 46 publications

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

Mass spectrometry for the detection of bioterrorism agents: from environmental to clinical applications

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