Related Experiment Video
Updated: Jul 20, 2025
Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza
Tanya Novak1,2,3, Jeremy Chase Crawford1,4,5, Georg Hahn6
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.
Insights
Early gene expression in children with severe influenza indicates risk for prolonged Multiple Organ Dysfunction Syndrome (MODS). Neutrophil degranulation genes predict worse outcomes, while protein metabolism genes correlate with recovery.
Area of Science:
- Pediatric critical care medicine
- Infectious diseases
- Molecular biology
Background:
- Influenza virus causes significant global disease burden, particularly in children.
- Multiple Organ Dysfunction Syndrome (MODS) is a severe, life-threatening complication of influenza infection.
Purpose of the Study:
- To investigate RNA expression differences in children with severe influenza and MODS.
- To identify potential biomarkers for predicting MODS severity and outcomes in pediatric influenza patients.
Main Methods:
- RNA expression of 469 candidate genes was measured in whole blood samples from 191 pediatric intensive care unit patients with severe influenza.
- Samples were collected upon admission and approximately seven days later for some patients.
- Gene expression data were analyzed using linear models, controlling for age and bacterial co-infections.
Main Results:
- Children with prolonged MODS (≥7 days) showed significant upregulation of nine neutrophil degranulation-associated mRNA transcripts near admission.
- These neutrophil-related transcripts predicted prolonged MODS or death.
- Genes involved in protein metabolism and adaptive immunity signaling pathways were associated with MODS recovery within a week.
Conclusions:
- Early increased expression of neutrophil degranulation genes is linked to worse clinical outcomes in pediatric influenza patients.
- Findings are consistent with observations in adult cohorts with influenza, sepsis, and ARDS.
- Specific gene expression patterns may serve as early indicators of MODS severity in children.
Background:
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.
Methods:
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).
Results:
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.
Conclusion:
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.
