A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia.
BACKGROUND
Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome.


METHODS
Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore.


RESULTS
The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection.


CONCLUSIONS
The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.
Grant P
GP
Parnell
Anthony S
AS
McLean
David R
DR
Booth
Nicola J
NJ
Armstrong
Marek
M
Nalos
Stephen J
SJ
Huang
Jan
J
Manak
Wilson
W
Tang
Oi-Yan
OY
Tam
Stanley
S
Chan
Benjamin M
BM
Tang
D000328:Adult; D000368:Aged; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000821:virology; D003422:Critical Care; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000175:diagnosis* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011024:Pneumonia, Viral / Q000175:diagnosis* / Q000821:virology*; D059467:Transcriptome; D015854:Up-Regulation