Transcriptional profile of PBMCs in patients with acute RSV or Influenza infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34205 | GEO | 2012/03/12
SECONDARY ACCESSION(S): PRJNA154245
REPOSITORIES: GEO
Similar Datasets
Project description:To study the transcriptional profile of patients with acute RSV or Influenza infection,children of median age 2.4 months (range 1.5-8.6) hospitalized with acute RSV and influenza virus infection were offered study enrollment after microbiologic confirmation of the diagnosis. Blood samples were collected from them within 42-72 hours of hospitalization. We excluded children with suspected or proven polymicrobial infections, with underlying chronic medical conditions (i.e congenital heart disease, renal insufficiency), with immunodeficiency, or those who received systemic steroids or other immunomodulatory therapies. The RSV cohort consisted of 51 patients with median age of 2 months (range 1.5-3.9) and the influenza cohort had 28 patients with median age of 5.5 months (range 1.4-21). Control samples were obtained from healthy children undergoing elective surgical procedures or at outpatient clinic visits. To exclude viral co-infections we performed nasopharyngeal viral cultures of all subjects. We recruited 10 control patients for the RSV cohort with median age of 6.7 months (range 5-10), and 12 control patients for the influenza cohort with median age of18.5 months (range 10.5-26). We used microarrays to obtain the transcriptional profile of PBMCs from patients with acute RSV or Influenza infection and compared these signatures with the transcriptional profile of primary airway epithelial cells infected with RSV or Influenza.
2012-03-12 | E-GEOD-34205 | biostudies-arrayexpress
Project description:Analysis of transcriptional profiles in whole blood from children < 2 years of age (and healthy matched controls) with RSV, rhinovirus and influenza infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity and that RSV infection induces a distinct host response compared with influenza and rhinovirus infection Total RNA extracted from whole blood (lysed in Tempus tubes) drawn from individual pediatric patients with acute RSV, influenza and Rhinovirus lower respiratory tract infection. A total of 241 samples are analyzed: 135 with acute RSV LRTI, 30 with Rhinovirus LRTI, 16 with influenza LRTI, 39 age-sex matched healthy controls and 21 samples obtained one month after the acute hospitalization in children with RSV. Samples GSM1226237-GSM1226272, which were hybridized to Platform GPL10558, were normalized separately from the other Samples in this Series, which were hybridized to Platform GPL6884. 'GSE38900_non-normalized_GSM1226237-GSM1226272.txt.gz' includes the non-normalized data for Samples GSM1226237-GSM1226272; 'GSE38900_non-normalized.txt.gz' includes the non-normalized data for the other Samples.
2013-11-12 | E-GEOD-38900 | biostudies-arrayexpress
Project description:Analysis of transcriptional profiles in whole blood from children < 2 years of age (and healthy matched controls) with RSV, rhinovirus and influenza infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity and that RSV infection induces a distinct host response compared with influenza and rhinovirus infection
2013-11-12 | GSE38900 | GEO
Project description:This was a prospective observational cohort study involving a convenience sample of previously healthy children <2 years of age with acute RSV infection as well as healthy non-infected age matched controls. The study was conducted at Nationwide Children’s Hospital (NCH; Columbus, OH) during four respiratory seasons, from 2011 to 2015. Children were enrolled at the NCH urgent care clinics, the emergency department or in the inpatient ward or intensive care unit (PICU). For the inpatients enrolled at ward or PICU the median time from admission to sample collection was 21.3h (interquartile range [IQR] 16.7 -37.6h). The majority of children had a confirmatory RSV test (either rapid antigen testing or PCR based) at enrollment per standard of care. In addition, the presence of RSV was confirmed by quantitative real time (qRT)-PCR in all study subjects. Healthy age-matched controls were enrolled during well-child visits or minor elective surgical procedures not involving the respiratory tract as described [Mejias 2013]. Exclusion criteria were as follows: documented bacterial co-infections, premature birth (<36 weeks of gestation), chronic or congenital medical conditions, and immunodeficiency. For healthy controls, additional exclusion criteria included: presence of fever or symptoms of respiratory tract infection within two weeks of enrollment.
2020-04-22 | GSE105450 | GEO
Project description:Respiratory 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. In 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. Severe 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. In conclusion, by 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. Samples were taken of 26 patients with acute RSV infections, divided into mild (n=9), moderate (n=9) and severe (n=8) disease. From moderate and severe diseased patients recovery samples were obtained as well.
2015-06-06 | E-GEOD-69606 | biostudies-arrayexpress
Project description:Respiratory 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. In 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. Severe 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. In conclusion, by 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.
2015-06-06 | GSE69606 | GEO
Project description:The objective of this study was to identify gene expression markers of disease severity in a cohort of RSV infected children Respiratory syncytial virus (RSV) is the number one pathogen causing lower respiratory tract infection that leads to hospitalization in young children. Despite growing insights in the disease pathogenesis, the clinical presentation in these children is highly variable and heterogeneous, and reliable markers predictive of disease progression are lacking. We characterized the host response to acute RSV infection to identify biomarkers associated with RSV disease and disease severity. Whole genome transcriptome was analysed early on the disease course in blood samples from otherwise healthy children <2 years of age, who were either hospitalized (n = 110) or evaluated as outpatients (n = 37) due to RSV infection. Age-matched non-RSV-infected healthy children (n = 51) were analysed in parallel. A clustering approach on the transcriptome data revealed biologically meaningful biomarkers associated with progression to severe RSV disease. Overall, the whole blood transcriptome pointed to alterations in frequency of specific immune cell types (neutrophils, T- and B-lymphocytes, NK cells, monocytes) in RSV-infected children. In addition, a cluster enriched for neutrophil degranulation genes, was highly correlated with clinical disease severity. The driver genes of this cluster (OLFM4, ELANE, MMP8, BPI, CEACAM8, LCN2, LTF and MPO) were selected and validated in independent existing transcriptomics datasets. We identified a set of genes involved in neutrophil degranulation as markers for RSV disease severity. Additional prospective studies using these markers are required to further confirm their value as predictive tool in routine clinical care.
2022-01-21 | GSE188427 | GEO
Project description:Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
2023-07-07 | GSE236877 | GEO
Project description:In order to understand the immunopathogenesis of severe influenza H1N1/09, we compared the whole blood RNA transcriptome of children hospitalised with H1N1/09 infection with that of children hospitalised with RSV or bacterial infection Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 v3 Beadchips. Observational, prospective study. Patients were recruited at or after presentation to hospital. Main inclusion criteria were presence of illness of sufficient severity to warrant blood tests for clinical reasons, in child aged <17 years. Patient numbers recruited were as follows: H1N1/09 infection (n=25) RSV (n=34) (n=21), and healthy paediatric controls (n=33). After exclusion of children with co-infections, numbers of arrays analysed in were as follows: H1N1/09 n=19; RSV n=22; bacterial infection n=18; controls n=33
2013-09-05 | E-GEOD-42026 | biostudies-arrayexpress
Project description:LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naM-CM-/ve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses. Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMistM-BM-., MedImmune) (n= 20) or TIV (FluzoneM-BM-., Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDCM-bM-^@M-^Ys recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.
2014-03-31 | E-GEOD-52005 | biostudies-arrayexpress