title: Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163.
abstract: OBJECTIVE
  Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia.
  
  
  METHODS
  Observational cohort study.
  
  
  METHODS
  Five university hospitals in Denmark.
  
  
  METHODS
  A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls.
  
  
  METHODS
  Samples were collected for biochemical analyses at the time of first positive blood culture.
  
  
  RESULTS
  sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25).
  
  
  CONCLUSIONS
  Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.
authors.affiliation: Department of Clinical Biochemistry, AS Aarhus University Hospital, Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Nina
authors.initials: N
authors.lastname: Weis
authors.forename: Christian
authors.initials: C
authors.lastname: Wejse
authors.forename: Henrik
authors.initials: H
authors.lastname: Nielsen
authors.forename: Svend Stenvang
authors.initials: SS
authors.lastname: Pedersen
authors.forename: Jørn
authors.initials: J
authors.lastname: Attermann
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexø
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D016470:Bacteremia / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011008:Pneumococcal Infections / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D012680:Sensitivity and Specificity; D013296:Streptococcus pneumoniae; D016019:Survival Analysis; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface