A groundbreaking gene expression assay that peers into the body's immune system to distinguish sepsis from non-infectious inflammation with unprecedented accuracy.
Imagine a medical condition so swift and deadly that it kills more people than breast cancer, prostate cancer, and AIDS combined. A condition where every single hour of delayed treatment increases mortality by 4-8%. This isn't a rare disease from a medical thriller—it's sepsis, and it's playing out in hospitals around the world every day.
Sepsis kills more people than breast cancer, prostate cancer, and AIDS combined.
Each hour of delayed treatment increases mortality by 4-8%.
Sepsis occurs when the body's response to an infection spirals out of control, causing life-threatening organ dysfunction. For critical care physicians, the fundamental challenge has always been determining whether a critically ill patient with systemic inflammation actually has an infection (sepsis) or is experiencing a non-infectious inflammatory condition (SIRS). This distinction is crucial—inappropriate antibiotic use in non-infected patients fuels antibiotic resistance, while delayed treatment in septic patients can be fatal.
Enter SeptiCyte™ LAB—a groundbreaking gene expression assay that peers into the body's immune system to distinguish sepsis from non-infectious inflammation with unprecedented accuracy. This revolutionary approach represents a paradigm shift from traditional methods that often provided ambiguous or delayed results.
Traditional sepsis diagnostics have primarily focused on trying to detect pathogens in the bloodstream through methods like blood cultures—a process that can take 24-72 hours and often returns negative results even when infection is present. SeptiCyte™ LAB takes a completely different approach by measuring the patient's immune response rather than hunting for pathogens.
The test works on an elegant principle: when facing different threats, our immune system activates specific genetic programs. The pattern of which genes are "turned on" or "turned off" creates a distinctive signature that can differentiate between infectious and non-infectious inflammation 1 .
Through extensive research analyzing thousands of patient samples, scientists discovered that the relative expression levels of four key genes—CEACAM4, LAMP1, PLAC8, and PLA2G7—create a reliable fingerprint for sepsis 1 .
Associated with immune cell function and differentiation
Plays a role in inflammation regulation
Involved in pathogen defense mechanisms
Involved in pathogen defense mechanisms
By measuring the RNA transcripts of these four genes from a small blood sample, SeptiCyte™ LAB generates a score that reflects the probability of sepsis, helping clinicians make more informed decisions during those critical early hours 1 .
| Score Range | Interpretation | Likelihood of Sepsis |
|---|---|---|
| 0.0 - 3.5 | Band 1 | Low |
| 3.6 - 5.0 | Band 2 | Indeterminate |
| 5.1 - 7.5 | Band 3 | High |
| 7.6 - 10.0 | Band 4 | Very High |
The convincing evidence for SeptiCyte™ LAB emerged from a comprehensive validation study published in the American Journal of Respiratory and Critical Care Medicine in 2018 . This ambitious project employed a prospective, observational, non-interventional design across seven clinical sites in the United States, eventually expanding to include patients from the large MARS consortium trial in the Netherlands.
critically ill adult patients enrolled
AUC for discriminating sepsis
Whole blood samples were collected from participants using specialized RNA-preservation tubes
Laboratory technicians processed the samples to extract high-quality RNA from white blood cells
The extracted RNA underwent reverse transcription quantitative polymerase chain reaction (RT-qPCR) to amplify and measure the four specific gene targets
A validated algorithm analyzed the expression levels of the four biomarkers to generate a SeptiScore® ranging from 0 to 10
| Diagnostic Method | Speed | Key Limitation | AUC in Validation Studies |
|---|---|---|---|
| Blood Cultures | 24-72 hours | Often negative despite infection | Not applicable |
| Procalcitonin | Hours | Affected by non-infectious inflammation | 0.70-0.80 |
| CRP | Hours | Non-specific inflammatory marker | 0.65-0.75 |
| SeptiCyte™ LAB | Hours | Requires specialized equipment | 0.82-0.89 |
The research demonstrated that the likelihood of sepsis versus non-infectious inflammation increased steadily with increasing test scores. Perhaps most notably, when researchers performed forward logistic regression analysis, they found that the diagnostic performance of SeptiCyte™ LAB improved only marginally when combined with other clinical and laboratory variables—including procalcitonin, a commonly used inflammatory biomarker . This suggests that the test provides independent diagnostic value that isn't redundant with existing assessments.
Building on the success of the laboratory-based test, the technology has evolved into SeptiCyte® RAPID—a fully automated, cartridge-based system that delivers results in approximately one hour with minimal hands-on time 3 . This revolutionary advancement places critical diagnostic information precisely where and when it's needed most: at the bedside of critically ill patients.
The RAPID version streamlined the original four-gene signature to a refined two-gene model focusing on PLAC8 and PLA2G7, which demonstrated equivalent discriminatory power 4 .
The COVID-19 pandemic unexpectedly demonstrated the broader utility of host response testing. Research published in Scientific Reports in 2023 revealed that SeptiCyte® RAPID could effectively stratify COVID-19 patients according to disease severity 9 .
for discriminating critical versus mild COVID-19 cases
Exceeding conventional biomarkers including CRP, lactate, IL-6, and D-dimer
This finding underscored the fundamental similarity between severe COVID-19 and traditional sepsis—both represent dysregulated immune responses that can lead to organ failure. The test's performance exceeded that of conventional biomarkers including CRP, lactate, IL-6, and D-dimer, suggesting its potential as a triage tool during pandemic surges when healthcare resources become stretched 9 .
| Component | Function | Specific Examples |
|---|---|---|
| RNA Preservation Tubes | Stabilizes RNA in blood samples immediately after collection | PAXgene Blood RNA Tubes |
| PCR Instrument Platform | Automated nucleic acid extraction, amplification, and detection | Biocartis Idylla™ System |
| Single-Use Test Cartridges | Integrated reagents and fluidics for automated testing | SeptiCyte® RAPID Cartridge |
| Gene Targets | Molecular markers of immune dysregulation | PLAC8, PLA2G7 (CEACAM4, LAMP1 in original version) |
| Reverse Transcriptase Enzyme | Converts RNA to DNA for amplification | SuperScript™ III Reverse Transcriptase |
| Algorithmic Scoring System | Interprets gene expression data as clinical probability | SeptiScore® (0-15 scale) |
The development of SeptiCyte™ LAB represents more than just another diagnostic test—it symbolizes a fundamental shift in how we approach complex medical conditions. By listening to the body's molecular responses rather than solely hunting for pathogens, this technology has opened new possibilities for precision medicine in critical care.
Recent research continues to explore applications in surgical patients 4 , pediatric populations, and other challenging scenarios where traditional diagnostics fall short. As the platform evolves toward even faster, more accessible formats, the potential to improve outcomes for the millions affected by sepsis annually grows exponentially.
The battle against sepsis has long been hampered by diagnostic uncertainty. With gene expression assays like SeptiCyte™ LAB, clinicians are now equipped with a powerful tool to cut through that uncertainty—transforming the approach to this devastating condition one genetic signature at a time.