Personalized Transcriptomics Reveals Heterogeneous Immunophenotypes in Children with Viral Bronchiolitis
Anya C Jones1,2, Denise Anderson1, Sally Galbraith3
11 Telethon Kids Institute and.
American Journal of Respiratory and Critical Care Medicine
|December 19, 2018
Summary
Infants susceptible to severe acute viral bronchiolitis (AVB) show dysregulated type 1 interferon signaling. This study identifies distinct immune profiles in infants versus children, highlighting slow innate immune maturation in susceptible infants.
Area of Science:
- Immunology
- Pediatrics
- Respiratory Medicine
Background:
- A subset of infants are highly susceptible to severe acute viral bronchiolitis (AVB).
- The underlying cellular and molecular mechanisms for this hypersusceptibility remain incompletely understood.
Purpose of the Study:
- To characterize the specific cellular and molecular mechanisms driving AVB in infants.
- To compare immune responses in circulating cells and local airway tissues between infants and children with AVB.
Main Methods:
- Collected peripheral blood mononuclear cells and nasal scrapings from infants and children with AVB.
- Utilized multiplex cytokine analysis, flow cytometry, and RNA-Seq for immune profiling.
- Applied group-level and personalized N-of-1-pathways analysis for data interpretation.
Main Results:
- Infant immune responses were dominated by monocyte-associated type 1 interferon and pro-inflammatory pathways.
- Children exhibited a combination of inflammation, growth/repair pathways, and T-helper/NK cell signaling.
- Nasal mucosal responses showed higher upregulation of interferon types 1-3 in infants compared to children.
Conclusions:
- Dysregulated type 1 interferon-dependent pathways are a key feature of AVB-susceptible infants.
- Susceptible infants and a subset of children may represent a distinct subgroup with delayed innate immune maturation.
- Personalized N-of-1-pathways analysis revealed age-independent AVB response subphenotypes.
Keywords:
-of-1-pathways analysisRNA-Seqacute viral bronchiolitisnasal mucosal airwaysperipheral blood mononuclear cellsMore Related Videos
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