Measuring the levels of RNA biomarkers in blood may help quickly differentiate sepsis from infection-negative systemic inflammation, according to research published this week in PLOS Medicine. Leo McHugh, Ph.D. of Immunexpress, Seattle, Washington, and colleagues describe the discovery and validation of a molecular classifier consisting of 4 RNA transcripts (SeptiCyte Lab), which in several selected patient cohorts was able to diagnose sepsis more accurately than procalcitonin or clinical parameters, and more quickly than blood culture.
McHugh and colleagues used microarray analysis to measure the RNA expression levels of thousands of genes in blood samples from a cohort of 74 patients with sepsis and 31 post-surgical patients with infection-negative systemic inflammation, thereby identifying the four genes (CEACAM4, LAMP1, PLA2G7, and PLAC8) that comprise the SeptiCyte Lab classifier. The researchers went on to validate the classifier in five additional cohorts from an independent Netherlands-based study, consisting of a total of 345 patients. In these validation cohorts, SeptiCyte Lab (which produced a result within 4 to 6 hours) was significantly better at differentiating patients with sepsis from patients with infection-negative systemic inflammation than was procalcitonin or clinical parameters available to a clinician within 24 hours of ICU admission. In the validation cohorts, using a specified threshold SeptiCyte Lab was able to correctly identify 90% of patients with sepsis, with a specificity of 60%.
The researchers note that validation in the Netherlands-based cohorts is preliminary, and that these results will need to be confirmed in larger studies that include patients from diverse geographic and hospital care settings.
With additional validation from further clinical studies, the authors believe this assay could be a clinically useful tool: "In combination with clinical parameters and clinical judgment, SeptiCyte Lab may provide physicians with enhanced confidence in therapeutic decision-making for patients with systemic inflammation."
This work was funded through Australian Commercial-Ready Proof of Concept Grants (COM04345 to RBB DV MRT and CAU05428 to RBB DV MRT AJS) and a Commercialisation Australia Proof of Concept Grant (CAU06263 to RBB RAB); and through the Center for Translational Molecular Medicine project MARS (grant 04I-201 to TVDP MB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have read the journal's policy, and declare the following: AJS JL PKK LVV BS MB OC MJS TVDP have no competing interests; TAS LM AR JTK TDY RAB RBB DJV MRT are employees and/or shareholders of Immunexpress, which holds the intellectual property in SeptiCyte Lab; JJP has no competing interests except for this: "In 2010 Immunexpress Inc. paid to the Adult Intensive Care Unit, Mater Health Services, Brisbane, Australia a sum of AUS $38,509 (thirty-eight thousand, five hundred and nine Australian dollars) as half-time temporary salary support for an ICU research coordinator to facilitate patient identification, recruitment and sample collection for 6 months from 20 May 2010."
McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ, et al. (2015) A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts. PLoS Med 12(12): e1001916. doi:10.1371/journal.pmed.1001916
Immunexpress, Seattle, Washington, United States of America
Biosurgical Ingenuity, Paddington, Queensland, Australia
Department of Intensive Care Medicine, Mater Health Services, South Brisbane, Queensland, Australia
Department of Pathology, Mater Health Services, South Brisbane, Queensland, Australia
School of Medicine, University of Queensland, St. Lucia, Queensland, Australia
Mater Research Institute, University of Queensland, St. Lucia, Queensland, Australia
Burns Trauma and Critical Care Research Centre, University of Queensland, St. Lucia, Queensland, Australia
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Herston, Queensland, Australia
Emphron Informatics, Toowong, Queensland, Australia
Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands
Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands
Division of Infectious Diseases, Academic Medical Center, Amsterdam, the Netherlands
Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, the Netherlands
Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, the Netherlands
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