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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory
Thomas J Mariani1,2, Xing Qiu3, ChinYi Chu1,2
1Division of Neonatology and Pediatric Molecular and Personalized Medicine Program.
Insights
Respiratory syncytial virus (RSV) severity in infants is linked to changes in CD4+ T-cell gene expression. Identifying these immune cell phenotypes could predict disease outcomes.
Area of Science:
- Immunology
- Genomics
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) is a common childhood infection, with 1-3% of cases leading to hospitalization.
- The study investigates the role of the adaptive immune system in determining RSV disease severity.
Purpose of the Study:
- To identify gene expression patterns in CD4+ T-lymphocytes that correlate with RSV disease severity.
- To explore potential biomarkers for predicting clinical outcomes in infants with RSV.
Main Methods:
- Studied infants with mild versus severe RSV illness, defined by respiratory rate and oxygen saturation.
- Performed RNA sequencing on purified CD4+ T cells to analyze gene expression.
- Utilized pathway analysis to identify biological processes associated with disease severity.
Main Results:
- Factors like gestational age, age at onset, environmental exposures, and breastfeeding were associated with RSV severity.
- CD4+ T-cell gene expression showed significant changes related to RSV illness severity.
- Key signaling pathways (JAK/STAT, prolactin, IL-9) were identified as correlates of severity.
Conclusions:
- Fundamental alterations in adaptive immune cell phenotypes are associated with RSV clinical severity.
- Gene expression profiling of CD4+ T cells offers insights into the mechanisms underlying RSV disease progression.
Background:
Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%-3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4+ T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity.
Methods:
Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO2) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4+ T cells was assessed by RNA sequencing.
Results:
Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B).
Conclusions:
These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.
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