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Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163
Holger Jon Møller1, Søren K Moestrup, Nina Weis
1Department of Clinical Biochemistry, AS Aarhus University Hospital, Denmark.
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.
Design:
Observational cohort study.
Setting:
Five university hospitals in Denmark.
Patients:
A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls.
Interventions:
Samples were collected for biochemical analyses at the time of first positive blood culture.
Measurements And Main 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.
Insights
Soluble CD163 (sCD163), a macrophage marker, predicts fatal outcomes in pneumococcal bacteremia patients under 75. Macrophage responses are impaired in older adults, making sCD163 a superior prognostic tool in younger patients.
Area of Science:
- Immunology
- Infectious Diseases
- Biochemistry
Background:
- Pneumococcal bacteremia is a serious infection.
- Macrophage activation markers may indicate disease severity and prognosis.
- Soluble CD163 (sCD163) is a novel macrophage-specific serum marker.
Purpose of the Study:
- To investigate sCD163 and other macrophage activation markers (neopterin, ferritin, transcobalamin, suPAR) as prognostic factors in pneumococcal bacteremia.
- To compare the prognostic value of these markers with C-reactive protein (CRP).
- To assess the influence of age on macrophage marker response and prognostic utility.
Main Methods:
- Observational cohort study involving 133 patients with S. pneumoniae bacteremia and 133 matched controls.
- Biochemical analyses of serum markers were performed at the time of diagnosis.
- Statistical analysis included correlation, comparison between groups, and multivariate logistic regression.
Main Results:
- sCD163 levels were significantly elevated in patients with pneumococcal bacteremia compared to controls and correlated with other macrophage markers.
- Increased sCD163 levels were associated with intensive care unit needs (hemodialysis, hypotension, mechanical ventilation).
- In patients under 75, sCD163 (cutoff 9.5 mg/L) and CRP (cutoff 1650 nmol/L) were significant predictors of fatal outcome, with sCD163 showing a higher relative risk (10.1 vs 7.0).
- Macrophage marker response was compromised in patients aged 75 and older.
- In patients under 75, sCD163 provided significant prognostic information, rendering other markers like ferritin, transcobalamin, neopterin, and suPAR non-significant when sCD163 and CRP were known.
Conclusions:
- Macrophage marker response is attenuated in elderly patients with pneumococcal bacteremia.
- In patients under 75 years old, sCD163 is a more potent predictor of fatal outcome than other assessed macrophage markers and C-reactive protein.