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Biomarkers hold important clues for RSV
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Children aged younger than 2 years who have respiratory syncytial virus are very likely to experience systemic activation of their interferon signaling networks, according to study data published online.
A study by John W. Belmont, MD, PhD, of the Baylor College of Medicine departments of molecular and human genetics and pediatrics, and colleagues reported on global gene expression data, derived from the whole blood cells of 21 children who had acute bronchiolitis and a positive rapid test for respiratory syncytial virus (RSV) and 37 controls. The children were recruited from the Texas Children’s Hospital ED.
John W. Belmont
“Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network,” the researchers said. “There was a significant down regulation of transcripts corresponding to antigen presentation.”
The researchers, including Infectious Diseases in Children Editorial Board member Pedro A. Piedra, MD,reported no significant differences in gene expression profiles between white and black infants.
The findings hold potential for future research because “these gene transcripts or their protein products could be promising biomarkers for acute RSV bronchiolitis in future prospective studies,” the researchers said, adding that this research is particularly important because current diagnostic methods for RSV lack sensitivity.
“Integrative systems biology and genetic studies represent an important new direction in infectious disease and vaccine research. Revisiting classic problems in infection and immunity using the latest genomics technologies is guaranteed to give new insights in pathogenesis and unrecognized host factors,” Belmont told Infectious Diseases in Children.
The researchers urged further study in the ED setting, with larger populations of patients.
Disclosure: The study was partially funded by NIH. Belmont serves on the ethics advisory board for Illumina Inc., with the consultant fee paid to Baylor College of Medicine.
John W. Belmont, MD, PhD, can be reached at 1100 Bates Ave, Houston, TX 77030; email: jbelmont@bcm.edu.
Perspective
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H. Cody Meissner, MD
RSV infection in young children ranges from a mild upper respiratory tract illness to severe lower tract disease with bronchiolitis, pneumonia and even respiratory failure. Several factors influence disease severity. Certain underlying conditions, such as chronic lung disease or age younger than 6 weeks, increase the risk of more severe disease. Certain strains or genotypes of RSV may be more virulent than other strains and cause more severe disease.
Some reports suggest that the greater the inoculum, the greater the likelihood of severe disease. But even among children without these risk factors, severe RSV disease occurs. A forth factor that contributes to variation in disease severity is the immune response of the host. Changes (single nucleotide polymorphisms) in genes involved in regulating innate immunity, chemotaxis and airway mucosal response may be associated with more severe disease. The report by Bucasas and colleagues addresses differences in gene expression in the white blood cells of children with RSV infection and controls.
The authors describe a profile of gene expression (up-regulation of genes such as those associated with antiviral functions and down-regulation of other genes associated with a protective response) in patients with acute RSV bronchiolitis, but not in controls. These observations support the theory that the acuity of RSV disease is due not only to direct virus- induced damage of the airways but also to the host’s immune response to the virus.
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