Host Biomarkers and Paediatric Infectious Diseases: From Molecular Profiles to Clinical Application

Brand, H. Kim; Hermans, Peter W. M.; Groot, Ronald de

doi:10.1007/978-1-4419-0981-7_2

Cited by 5 publications

(4 citation statements)

References 52 publications

(50 reference statements)

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“…The advantage of measuring markers in plasma is the ease of implementation, speed, reproducibility and standardization. However, innovative techniques enable rapid analysis of the expression of multiple genes at transcriptional level in the near future [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

et al. 2015

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BackgroundRespiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making.MethodsIn a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort.ResultsSevere RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age.ConclusionBy combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

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Section: Discussionmentioning

confidence: 99%

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

et al. 2015

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“…Furthermore, markers for disease severity are also important for research purposes to study effects of interventions, such as treatment. Although currently no biomarkers at transcription level are available in the clinic, because the processing is time consuming, innovative techniques may enable rapid analysis of the expression of multiple genes at transcriptional level in the near future [Brand et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Use of MMP‐8 and MMP‐9 to assess disease severity in children with viral lower respiratory tract infections

Brand

Ahout

Groot

et al. 2012

Journal of Medical Virology

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Matrix metalloproteinases (MMPs) play an important role in respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. It was hypothesized that MMP-8 and MMP-9 may function as biological markers to assess disease severity in viral lower respiratory tract infections in children. MMP-8 and MMP-9 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) and granulocytes obtained in both the acute and recovery phase from 153 children with mild, moderate, and severe viral lower respiratory tract infections were determined using real-time PCR. In addition, MMP-8 and MMP-9 concentrations in blood and nasopharyngeal specimens were determined during acute mild, moderate, and severe infection, and after recovery using ELISA. Furthermore, PBMCs and neutrophils obtained from healthy volunteers were stimulated with RSV, LPS (TLR4 agonist), and Pam3Cys (TLR2 agonist) in vitro. Disease severity of viral lower respiratory tract infections in children is associated with increased expression levels of the MMP-8 and MMP-9 genes in both PBMCs and granulocytes. On the contrary, in vitro experiments showed that MMP-8 and MMP-9 mRNA and protein expression in PBMCs and granulocytes is not induced by stimulation with RSV, the most frequent detected virus in young children with viral lower respiratory tract infections. These data indicate that expression levels of the MMP-8 and MMP-9 genes in both PBMCs and neutrophils are associated with viral lower respiratory tract infections disease severity. These observations justify future validation in independent prospective study cohorts of the usefulness of MMP-8 and MMP-9 as potential markers for disease severity in viral respiratory infections.

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“…Several biomarkers, such as the inflammatory mediator proteins IP-10 and CXCL11, are thought to activate other cells that provide a favorable environment for pneumonia infection. While influenza infection cannot be avoided, the progression to pneumonia can be stopped if these biomarkers are detected early enough after viral infection (Brand et al, 2010). However, due to the complexity of serum, the sensitivity of detection for this panel can be too low to make an accurate diagnosis.…”

Section: Use Of Nanotrap Particles For Host Biomarker Discovery Applimentioning

confidence: 99%

The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics

et al. 2014

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Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays.

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Host Biomarkers and Paediatric Infectious Diseases: From Molecular Profiles to Clinical Application

Cited by 5 publications

References 52 publications

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

Use of MMP‐8 and MMP‐9 to assess disease severity in children with viral lower respiratory tract infections

The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics

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