title: Olfactomedin-4 Is a Candidate Marker for a Pathogenic Neutrophil Subset in Septic Shock.
abstract: OBJECTIVE
  Heterogeneity in sepsis-related pathobiology presents a significant challenge. Resolving this heterogeneity presents an opportunity to understand pathobiology and improve patient care. Olfactomedin-4 is a neutrophil subset marker and may contribute to sepsis heterogeneity. Our objective was to evaluate the expression of olfactomedin-4 and characterize neutrophil heterogeneity in children with septic shock.
  
  
  METHODS
  Single-center, prospective cohort, as well as secondary analysis of existing transcriptomic and proteomic databases.
  
  
  METHODS
  Tertiary care PICU.
  
  
  METHODS
  Patients from 5 days to 18 years old with septic shock were enrolled. Data collected included the expression of olfactomedin-4 messenger RNA, serum protein concentrations, and percentage of neutrophils that express olfactomedin-4.
  
  
  METHODS
  None.
  
  
  RESULTS
  Secondary analysis of existing transcriptomic data demonstrated that olfactomedin-4 is the most highly expressed gene in nonsurvivors of pediatric septic shock, compared with survivors. Secondary analysis of an existing proteomic database corroborated these observations. In a prospectively enrolled cohort, we quantified the percentage of olfactomedin-4+ neutrophils in patients with septic shock. Patients with a complicated course, defined as greater than or equal to two organ failures at day 7 of septic shock or 28-day mortality, had a higher percentage of olfactomedin-4+ neutrophils, compared with those without a complicated course. By logistic regression, the percentage of olfactomedin-4+ neutrophils was independently associated with increased risk of a complicated course (odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.024).
  
  
  CONCLUSIONS
  Olfactomedin-4 identifies a subpopulation of neutrophils in patients with septic shock, and those with a high percentage of olfactomedin-4+ neutrophils are at higher risk for greater organ failure burden and death. Olfactomedin-4 might serve as a marker of a pathogenic neutrophil subset in patients with septic shock.
authors.affiliation: 1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Children's Hospital Research Foundation, Cincinnati, OH.2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.3Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Children's Hospital Research Foundation, Cincinnati, OH.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Alder
authors.forename: Amy M
authors.initials: AM
authors.lastname: Opoka
authors.forename: Patrick
authors.initials: P
authors.lastname: Lahni
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D030541:Databases, Genetic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007958:Leukocyte Count; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology; D009504:Neutrophils / Q000737:chemistry*; D011446:Prospective Studies; D020543:Proteome; D012333:RNA, Messenger / Q000097:blood*; D012772:Shock, Septic / Q000097:blood* / Q000150:complications / Q000235:genetics; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C454127:OLFM4 protein, human; D020543:Proteome; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor