Feature Articles

Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum*

Wong, Hector R. MD; Cvijanovich, Natalie MD; Allen, Geoffrey L. MD; Lin, Richard MD; Anas, Nick MD; Meyer, Keith MD; Freishtat, Robert J. MD; Monaco, Marie BSN; Odoms, Kelli BS; Sakthivel, Bhuvaneswari MS; Shanley, Thomas P. MD for the Genomics of Pediatric SIRS/Septic Shock Investigators

Author Information

From the Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Research Foundation, Department of Pediatrics (HRW, MM, KO, BS), University of Cincinnati College of Medicine, Cincinnati, OH; Children’s Hospital and Research Center Oakland (NC), Oakland, CA; Children’s Mercy Hospital (GLA), Kansas City, MO; The Children’s Hospital of Philadelphia (RL), Philadelphia, PA; Children’s Hospital of Orange County (NA), Orange, CA; Miami Children’s Hospital (KM), Miami, FL; Children’s National Medical Center (RJF), Washington DC; and C.S. Mott Children’s Hospital at the University of Michigan (TPS), Ann Arbor, MI.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ccmjournal.org).

Supported by a grant from the National Institute of General Medical Sciences (RO1 GM064619).

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: [email protected]

Critical Care Medicine 37(5):p 1558-1566, May 2009. | DOI: 10.1097/CCM.0b013e31819fcc08

Abstract

Objectives:

To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum.

Design:

Prospective observational study involving microarray-based bioinformatics.

Setting:

Multiple pediatric intensive care units in the United States.

Patients:

Children ≤10 years of age: 18 normal controls, 22 meeting criteria for SIRS, 32 meeting criteria for sepsis, and 67 meeting criteria for septic shock on day 1. The available day 3 samples included 20 patients still meeting sepsis criteria, 39 patients still meeting septic shock criteria, and 24 patients meeting the exclusive day 3 category, SIRS resolved.

Interventions:

None other than standard care.

Measurements and Main Results:

Longitudinal analyses were focused on gene expression relative to control samples and patients having paired day 1 and day 3 samples. The longitudinal analysis focused on up-regulated genes revealed common patterns of up-regulated gene expression, primarily corresponding to inflammation and innate immunity, across all patient groups on day 1. These patterns of up-regulated gene expression persisted on day 3 in patients with septic shock, but not to the same degree in the other patient classes. The longitudinal analysis focused on down-regulated genes demonstrated gene repression corresponding to adaptive immunity-specific signaling pathways and was most prominent in patients with septic shock on days 1 and 3. Gene network analyses based on direct comparisons across the SIRS, sepsis, and septic shock spectrum, and all available patients in the database, demonstrated unique repression of gene networks in patients with septic shock corresponding to major histocompatibility complex antigen presentation. Finally, analyses focused on repression of genes corresponding to zinc-related biology demonstrated that this pattern of gene repression is unique to patients with septic shock.

Conclusions:

Although some common patterns of gene expression exist across the pediatric SIRS, sepsis, and septic shock spectrum, septic shock is particularly characterized by repression of genes corresponding to adaptive immunity and zinc-related biology.