Objectives
Heterogeneity in sepsis-related pathobiology presents a significant challenge. Resolving this heterogeneity presents an opportunity to understand pathobiology and improve patient care. Olfactomedin-4 (OLFM4) is a neutrophil subset marker and may contribute to sepsis heterogeneity. Our objective was to evaluate the expression of OLFM4 and characterize neutrophil heterogeneity in children with septic shock.
Design
Single-center, prospective cohort, as well as secondary analysis of existing transcriptomic and proteomic databases.
Setting
Tertiary care pediatric intensive care unit.
Patients
Patients from age 5 days to 18 years with septic shock were enrolled. Data collected included the expression of OLFM4 mRNA, serum protein concentrations and percentage of neutrophils that express OLFM4.
Interventions
None.
Measurements and Main Results
Secondary analysis of existing transcriptomic data demonstrated that OLFM4 is the most highly expressed gene in non-survivors of pediatric septic shock, compared to survivors. Secondary analysis of an existing proteomic database corroborated these observations. In a prospectively enrolled cohort, we quantified the percentage of OLFM4+ neutrophils in patients with septic shock. Patients with a complicated course, defined as ≥2 organ failures at day 7 of septic shock or 28-day mortality, had a higher percentage of OLFM4+ neutrophils, compared to those without a complicated course. By logistic regression, the percentage of OLFM4+ neutrophils was independently associated with increased risk of a complicated course (O.R. 1.09, 95% C.I. 1.01 to 1.17, p = 0.024).
Conclusions
OLFM4 identifies a subpopulation of neutrophils in patients with septic shock, and those with a high percentage of OLFM4+ neutrophils are at higher risk for greater organ failure burden and death. OLFM4 might serve as a marker of a pathogenic neutrophil subset in patients with septic shock.