A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia

Grant P Parnell,Wilson Tang,Jan Manak,Marek Nalos,Nicola J Armstrong,Benjamin M Tang,Stephen J Huang,Oi-Yan Tam,Anthony S Mclean,Stanley Chan,David R Booth

doi:10.1186/cc11477

Abstract

IntroductionDiagnosis 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.MethodsWhole-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.ResultsThe 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.ConclusionsThe 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.

Highlights

Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status
No difference in the severity of illness was found for patients in the bacterial pneumonia compared with the H1N1 influenza A pneumonia group (P = 0.82)
We have identified a T-cell-dominant gene-expression signature that is associated with the host response to severe influenza pneumonia

Summary

Introduction

Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. The clinical signs and symptoms of bacterial and viral pneumonia can overlap and are often confounded by underlying conditions such as immunosuppression and extrapulmonary complications [7,8,9] When these individuals present with community-acquired pneumonia, it is difficult to determine which organism is the causative pathogen (bacterial versus viral). We showed that changes in this immune response correlate well with the progression to respiratory failure in infected patients. The aim of this study was to investigate whether a gene-expression signature is present in individuals with severe influenza pneumonia, and whether this immune-response signature is distinct from other conditions that share a similar clinical presentation, such as bacterial pneumonia or systemic inflammation due to noninfectious causes

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