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Published on: August 12, 2020
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock
Hector R Wong1, Natalie Cvijanovich, Geoffrey L Allen
1Department of Pediatrics, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. hector.wong@cchmc.org
Insights
Pediatric septic shock uniquely represses adaptive immunity and zinc-related genes, differing from systemic inflammatory response syndrome (SIRS) and sepsis. These gene expression patterns offer insights into critical illness in children.
Area of Science:
- Pediatric critical care medicine
- Molecular biology
- Genomics
Background:
- Pediatric septic shock is a life-threatening condition with complex biological underpinnings.
- Understanding genome-wide gene expression is crucial for deciphering the pathophysiology of pediatric critical illnesses.
Purpose of the Study:
- To investigate genome-level expression profiles in critically ill children with systemic inflammatory response syndrome (SIRS), sepsis, and septic shock.
- To identify distinct molecular signatures associated with the spectrum of pediatric critical illness.
Main Methods:
- Prospective observational study utilizing microarray-based bioinformatics.
- Analysis of gene expression in children aged <=10 years, categorized into normal controls, SIRS, sepsis, and septic shock groups.
- Longitudinal analysis of gene expression on days 1 and 3, comparing patient groups and control samples.
Main Results:
- Common up-regulated gene expression patterns related to inflammation and innate immunity were observed across all patient groups.
- Persistent up-regulation of inflammatory genes was noted in septic shock patients on day 3.
- Down-regulated gene expression linked to adaptive immunity and major histocompatibility complex antigen presentation was prominent in septic shock.
- Repression of zinc-related genes was identified as a unique characteristic of pediatric septic shock.
Conclusions:
- While SIRS, sepsis, and septic shock share some inflammatory gene expression patterns, septic shock exhibits unique repression of adaptive immunity and zinc-related genes.
- These distinct molecular signatures may provide targets for understanding and treating pediatric septic shock.
Objectives:
To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum.
Design:
Prospective observational study involving microarray-based bioinformatics.
Setting:
Multiple pediatric intensive care units in the United States.
Patients:
Children
Interventions:
None other than standard care.
Measurements And Main Results:
Longitudinal analyses were focused on gene expression relative to control samples and patients having paired day 1 and day 3 samples. The longitudinal analysis focused on up-regulated genes revealed common patterns of up-regulated gene expression, primarily corresponding to inflammation and innate immunity, across all patient groups on day 1. These patterns of up-regulated gene expression persisted on day 3 in patients with septic shock, but not to the same degree in the other patient classes. The longitudinal analysis focused on down-regulated genes demonstrated gene repression corresponding to adaptive immunity-specific signaling pathways and was most prominent in patients with septic shock on days 1 and 3. Gene network analyses based on direct comparisons across the SIRS, sepsis, and septic shock spectrum, and all available patients in the database, demonstrated unique repression of gene networks in patients with septic shock corresponding to major histocompatibility complex antigen presentation. Finally, analyses focused on repression of genes corresponding to zinc-related biology demonstrated that this pattern of gene repression is unique to patients with septic shock.
Conclusions:
Although some common patterns of gene expression exist across the pediatric SIRS, sepsis, and septic shock spectrum, septic shock is particularly characterized by repression of genes corresponding to adaptive immunity and zinc-related biology.