A study published this week in PLOS Medicine reveals profound systemic dysregulation of the immune response induced by RSV infection in young children and suggest that molecular markers might be able to predict disease severity.
RSV is responsible for a substantial fraction of serious respiratory infections and deaths among young children worldwide and a top candidate for vaccine development.
A team of researchers led by Asuncion Mejias and Octavio Ramilo, both from The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, examined the global gene expression patterns in blood samples from four different cohorts of children who were hospitalized with lower respiratory tract infections.
They found that children who are ill with RSV infections have a characteristic gene expression pattern that is different not only from healthy children but also from children infected with either influenza virus or human rhinovirus, two other common causes of lower respiratory tract disease.
This pattern, which the researchers called the RSV biosignature, could reliably identify children with RSV infections in different settings. From it, they derived a genomic "severity score" that correlated with clinical indices of disease severity, and with length of hospitalization and need for supplemental oxygen.
The RSV biosignature also provided insights into the status of the immune system in the sick children: RSV infection was associated with elevated levels of some inflammation genes as well as suppression of non-specific immune system genes and reduced expression of specific B and T cell genes. This was particularly evident in infants under 6 months of age.
The authors conclude that "Blood RNA profiles of infants with RSV lower respiratory tract infections allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity" and say their study "opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets."
In an accompanying Perspective, Peter Openshaw agrees that "this study moves the field several steps towards the clinical use of transcriptomic profiling in the diagnosis and prognostication of children with acute respiratory infections" but also cautions that "the peripheral blood may not be telling the whole story and needs to be complemented by detailed studies of the response in the respiratory tract".
Research Article
Funding: This work was supported by the National Institute of Allergy and Infectious Diseases (Grant numbers: U19AI057234; U19AI089987), the RGK Foundation, and Nationwide Children's Hospital intramural funds. The sponsors had no role in study design, data collection, data analysis, data interpretation, decision to publish, or preparation of the manuscript.
Competing Interests: In the last 3 years, OR has had financial relations with companies that are involved with respiratory viruses research or product as follows: Advisory boards: Gilead, Abbvie, Alios, Quidel; Honoraria for Lectures and Co-Chair Medical Conferences: Abbvie; Cover part of travel expenses to present clinical study at a scientific conference: MedImmune; Research Grant: Abbott Molecular. In the last 3 years, AM has had relations with companies that are involved with respiratory viruses research or product as follows: Advisory Boards: Alios, Janssen Infectious Diseases BVBA; Honoraria for Lectures at CME Conferences: Abbvie; Research Grant: Gilead. All other authors have declared that no competing interest exist.
Citation: Mejias A, Dimo B, Suarez NM, Garcia C, Suarez-Arrabal MC, et al. (2013) Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection. PLoS Med 10(11): e1001549. doi:10.1371/journal.pmed.1001549
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Contact:
Asuncion Mejias or Octavio Ramilo
Center for Vaccines and Immunity,
The Research Institute at Nationwide Children's Hospital
UNITED STATES
001 614 355 2949 or 001 614 722 2735
asuncion.mejias@nationwidechildrens.org; octavio.ramilo@nationwidechildrens.org
Journal
PLoS Medicine