Rapid Molecular Host-Response Assay May Improve Diagnosis of Sepsis

A microarray assay that measures classifier RNA transcript biomarkers in blood may help quickly differentiate sepsis from infection-negative systemic inflammation (INSI) in critically ill patients, according to a new study.

A team led by Leo McHugh, PhD, of Immunexpress Inc. (Seattle, WA, USA), reports 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.

Dr. McHugh and colleagues used microarray analysis to measure RNA expression levels of thousands of genes in blood samples from a cohort of 74 patients with sepsis and 31 post-surgical patients with INSI, thereby identifying the four genes (CEACAM4, LAMP1, PLA2G7, and PLAC8) that comprise the SeptiCyte Lab classifier. The researchers further validated the classifier in 5 additional cohorts from an independent Netherlands-based study, consisting of a total of 345 patients. In these cohorts, SeptiCyte Lab, which produced a result within 4–6 hours, was significantly better at differentiating patients with sepsis from patients with INSI 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%.

Validation in the Netherlands-based cohorts is preliminary, so larger clinical studies are needed that include patients from diverse geographic and hospital care settings. The researchers suggested that this assay could become 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."

The study, by McHugh L et al., was published December 8, 2015, in the journal PLOS Medicine.

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