Cord Blood Gene Expression in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis (original) (raw)
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Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis
2006
Background: Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR) both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease.
Journal of Infectious Diseases, 2011
Background. Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants. Methods. We obtained blood and BAL samples from 20 infants with severe RSV bronchiolitis and 8 healthy control infants. Neutrophil RSV F, G, and N proteins, RSV N genomic RNA, and messenger RNA (mRNA) were quantified. Results. RSV proteins were found in BAL and blood neutrophils in infants with RSV disease but not in neutrophils from healthy infants. BAL and blood neutrophils from infants with RSV disease, but not those from healthy infants, expressed RSV N genomic RNA, indicating uptake of whole virus; 17 of 20 BAL and 8 of 9 blood neutrophils from patients expressed RSV N mRNA. Conclusions. This work shows, for the first time, the presence of RSV proteins and mRNA transcripts within BAL and blood neutrophils from infants with severe RSV bronchiolitis.
Reduced Nasal Viral Load and IFN Responses in Infants with RSV Bronchiolitis and Respiratory Failure
American journal of respiratory and critical care medicine, 2018
Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. Infants with viral bronchiolitis necessitating admission (n=55) were recruited from a paediatric centre during 2016/17. Of these, 30 were RSV infected (18 'moderate', and 12 mechanically ventilated 'severe'). Nasal fluids were sampled frequently over time using nasosorption devices and nasophayngeal aspiration (NPA). Hierarchical clustering of time weighted averages (TWA) was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. Unexpectedly, cases of severe RSV bronchiolitis had lower nasal viral loads and reduced inter...
Open Forum Infectious Diseases, 2018
Background Data are controversial regarding the role of viral load and the host immune response in the severity of respiratory syncytial virus (RSV) infection. The objective of this study was t. o analyze the relationship between viral load (VL) and host cytokine responses with RSV life-threatening disease (LTD). Methods Prospective cohort study including previously healthy infants <12 months, hospitalized with a first RSV infection in 2017. Viral titers were assessed by qPCR and cytokine levels measured in nasopharyngeal aspirates obtained on admission. All patients with LTD were admitted to the intensive care unit. Results Fifty-one patients, median age 3 months (IQR 2–4), 29(56.9%) male. Eight developed LTD (1,569 LTD cases/10,000 RSV-hospitalizations/year [95% CI 702–2.859]). Antibiotic prescription was significantly higher (42.9 vs. 87.5%, P < 0.001) and length of hospitalization significantly prolonged (5.2 ± 1.9 vs. 16.1 ± 12.7 days, P < 0.001) in infants with LTD. N...
Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection
Journal of Allergy and Clinical Immunology, 2009
Background: It has been claimed that an early respiratory syncytial virus (RSV) infection can induce asthma and recurrent wheezing. Objective: We addressed the question of whether infants contracting an early RSV infection differ from healthy children in their cytokine production at birth. Methods: In a prospective cohort study cord blood samples were collected from 1084 newborns during autumn 2001. Of 47 of these newborns with subsequent virologically confirmed RSV infection before 6 months of age, 24 had enough cells for stimulation in cord blood samples (14 of those were hospitalized). Twenty-eight children had other respiratory virus infections (16 with enough cells), and samples from 48 healthy children of the 1084 total served as control specimens. Stimulated cytokine production of mononuclear cells was measured. The responses in the groups were evaluated by means of factor analysis. Results: The infants hospitalized for RSV infection had higher LPS-stimulated combined IL-6 and IL-8 responses than the infants treated as outpatients (P 5 .005) or the healthy control subjects (P 5 .02). The hospitalized patients with RSV showed lower IL-1b, IL-2, IL-4, IL-5, and IL-10 responses than those treated as outpatients (P 5 .02). High IL-6 and IL-8 responsiveness predicted a severe RSV infection (odds ratio, 2.20; 95% CI, 1.17-4.14; P 5 .01). The unstimulated cytokine responses at birth did not differ between the patients and healthy control subjects. Conclusion: The results suggest that natural differences in innate immunity predispose children to severe RSV infection rather than the infection modifying immune responses in childhood. (J Allergy Clin Immunol 2009;124:52-8.) Abbreviations used CBMC: Cord blood mononuclear cell RSV: Respiratory syncytial virus Standardized factor-score variables derived from the loadings were used in the logistic regression analyses.
Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants
Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients. Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection that in some instances may have a fatal outcome. Especially infants, elderly and patients with underlying chronic disorders suffer from severe RSV infections 1,2. In infants, RSV is the leading cause of lower respiratory tract infections (LRTI) and is responsible for 80% of acute bronchiolitis cases 3. RSV infections pose a huge burden on society in terms of disease, logistics and socioeconomic sequelae. There is an unmet need for an RSV vaccine, despite considerable research efforts no licensed vaccine has been developed. In industrialized countries, 1–5% of infants with RSV infection are hospitalized 4–7. Some of these infants yet suffer from severe disease upon admittance, while others are admitted without severe symptoms since the course of bronchiolitis is highly variable and the need for supportive care cannot be predicted 8,9. Several risk factors for developing severe RSV disease in infants have been identified, including preterm birth, young age, sex and environmental factors like in-house smoking 10. Notwithstanding these known risk factors, current medical practice does not allow accurate prediction of whether an infant will further progress to severe RSV disease or not and could even be sent home safely. Genomic technologies have contributed to study the virus-host interaction , including virus discovery, pathogenesis studies, the design of antiviral strategies and identification of biomarkers to support clinical management of infectious diseases 11–14. For RSV infections, this has supported the characterization of vaccine-induced skewed host responses upon infection 15,16. Meijas et al. 17 recently used
American Journal of Respiratory and Critical Care Medicine
Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both. Objectives: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. Methods: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. Measurements and Main Results: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-g and CC chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P , 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. Conclusions: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/ IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells.