What is Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)?
Soluble TREM-1 (sTREM-1) is a shed form of a cell surface receptor from the immunoglobulin superfamily that amplifies inflammatory responses when neutrophils and monocytes encounter bacterial or fungal infections, but it lacks sufficient specificity for clinical use because it also elevates in non-infectious inflammation. 1
Biological Mechanism
TREM-1 is strongly expressed on neutrophils and monocytes that infiltrate tissues invaded by bacteria or fungi, functioning as a major amplifier of innate immune responses 1, 2
The soluble form (sTREM-1) is released into biological fluids including blood, bronchoalveolar lavage fluid (BALF), and cerebrospinal fluid, where it can be measured by ELISA or immunoblot techniques 1
sTREM-1 acts as an amplifier of myeloid cell inflammatory responses at pathologic sites, contributing to both protective immunity and potentially harmful inflammation 2
Clinical Context and Limitations
Diagnostic Performance in Sepsis
In hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), sTREM-1 measured in BALF demonstrates only moderate accuracy with a sensitivity of 84% and specificity of 49%, falling well below the 90% threshold needed for clinical decision-making 1
The Infectious Diseases Society of America and American Thoracic Society strongly recommend against using BALF sTREM-1 plus clinical criteria to guide antibiotic initiation in suspected HAP/VAP, favoring clinical criteria alone instead 1
In sepsis diagnosis, sTREM-1 shows variable performance with sensitivity of 70% and specificity of 60% for distinguishing septic from non-infectious SIRS patients, performing worse than C-reactive protein and ESR 3
Critical Specificity Problem
sTREM-1 elevates in non-infectious causes of inflammation, making it unreliable for distinguishing infection from sterile inflammation 1
The lack of standardized assays and widely varying cutoff values (5 to 900 pg/mL) across studies prevents consistent clinical application 1
In Alzheimer's disease research, sTREM2 (a related molecule) is released by peripheral leukocytes, highlighting that soluble TREM measurements may not specifically reflect the intended tissue compartment 1
Prognostic Value
Despite poor diagnostic specificity, sTREM-1 shows some prognostic utility:
Higher baseline sTREM-1 levels correlate with mortality in severe sepsis, with levels remaining elevated in non-survivors while decreasing in survivors over time 4, 5
In neonatal sepsis, sTREM-1 cutoff of 1100 pg/mL predicts survival with 100% sensitivity and 97% specificity, though this requires validation 6
sTREM-1 correlates with Sequential Organ Failure Assessment (SOFA) scores more strongly than CRP or procalcitonin, reflecting disease severity 5
In cancer, high TREM-1 expression in tumor-infiltrating macrophages and elevated soluble TREM-1 correlate with aggressive tumor behavior and poor survival 2
Practical Clinical Implications
Do not use sTREM-1 measurements to guide antibiotic initiation decisions in suspected HAP/VAP or other infections, as the false-positive and false-negative rates are unacceptably high for clinical decision-making 1
The primary clinical pitfall is over-interpreting elevated sTREM-1 as definitive evidence of bacterial infection, when it may simply reflect non-infectious inflammation, tissue damage, or other inflammatory stimuli 1
sTREM-1 remains primarily a research tool rather than a validated clinical biomarker, with potential future applications pending assay standardization and better understanding of its tissue-specific versus systemic contributions 1, 2