Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 31, Pages 12792-12797Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1302968110
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Funding
- National Cancer Institute [P30 CA91842]
- Institute for Clinical and Translational Sciences/Clinical and Translational Sciences Award from the National Center for Research Resources, National Institutes of Health [UL1RR024992]
- National Institutes of Health Roadmap for Medical Research
- National Institute of Allergy and Infectious Diseases [1UAH2AI083266-01]
- National Institutes of Health-National Center for Research Resources
- Washington University Institute for Clinical and Translational Sciences [UL1 RR024992]
- National Institute of Child Health and Human Development [T32HD049338]
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Viral infections are common causes of fever without an apparent source in young children. Despite absence of bacterial infection, many febrile children are treated with antibiotics. Virus and bacteria interact with different pattern recognition receptors in circulating blood leukocytes, triggering specific host transcriptional programs mediating immune response. Therefore, unique transcriptional signatures may be defined that discriminate viral from bacterial causes of fever without an apparent source. Gene expression microarray analyses were conducted on blood samples from 30 febrile children positive for adenovirus, human herpesvirus 6, or enterovirus infection or with acute bacterial infection and 22 afebrile controls. Blood leukocyte transcriptional profiles clearly distinguished virus-positive febrile children from both virus-negative afebrile controls and afebrile children with the same viruses present in the febrile children. Virus-specific gene expression profiles could be defined. The IFN signaling pathway was uniquely activated in febrile children with viral infection, whereas the integrin signaling pathway was uniquely activated in children with bacterial infection. Transcriptional profiles classified febrile children with viral or bacterial infection with better accuracy than white blood cell count in the blood. Similarly accurate classification was shown with data from an independent study using different microarray platforms. Our results support the paradigm of using host response to define the etiology of childhood infections. This approach could be an important supplement to highly sensitive tests that detect the presence of a possible pathogen but do not address its pathogenic role in the patient being evaluated.
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