title: Monocyte expression and soluble levels of the haemoglobin receptor (CD163/sCD163) and the mannose receptor (MR/sMR) in septic and critically ill non-septic ICU patients.
abstract: BACKGROUND
  The diagnosis of sepsis is challenging and there is an unmet need for sensitive and specific diagnostic and prognostic biomarkers. Following activation of macrophages and monocytes, the haptoglobin-haemoglobin receptor (CD163) and the mannose receptor (MR) are shed into the circulation (sCD163 and sMR).
  
  
  OBJECTIVE
  We investigated monocyte expression of CD163 and MR, and levels of sCD163 and sMR in septic and non-septic patients, and in healthy controls. We hypothesised that these receptors are elevated during sepsis and can be used diagnostic and prognostic.
  
  
  METHODS
  Twenty-one patients with severe sepsis or septic shock and 15 critically ill non-septic patients were included in this prospective observational study at three ICUs at Aarhus University Hospital and Randers Regional Hospital, Denmark. Fifteen age- and gender-matched healthy volunteers served as controls. Levels of sCD163 and sMR were measured using a sandwich ELISA and monocyte expression of CD163 and MR was evaluated by flow cytometry during the first four days of ICU stay. The diagnostic and prognostic values of the receptors were assessed using AUROC curves.
  
  
  RESULTS
  At ICU admission and during the observation period, monocyte expression of CD163 and levels of sCD163 and sMR were significantly higher in septic patients compared with non-septic patients and healthy controls (p<0.01 for all comparisons). Monocytes did not express MR. The diagnostic values estimated by AUROC were 1.00 for sMR, 0.95 for sCD163, 0.87 for CRP, and 0.75 for monocyte-bound CD163. Among the septic patients, monocyte expression of CD163 was higher in non-survivors compared with survivors at ICU admission (p = 0.02) and during the observation period (p = 0.006). The prognostic value of monocyte-bound CD163 estimated by AUROC at ICU admission was 0.82.
  
  
  CONCLUSIONS
  The macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new biomarker of sepsis.
authors.affiliation: Aarhus University Hospital, Department of Anaesthesiology and Intensive Care, Aarhus C, Denmark; Randers Regional Hospital, Department of Anaesthesiology and Intensive Care, Randers, Denmark.
authors.forename: Anders G
authors.initials: AG
authors.lastname: Kjærgaard
authors.affiliation: Aarhus University Hospital, Department of Clinical Biochemistry, Aarhus C, Denmark.
authors.forename: Sidsel
authors.initials: S
authors.lastname: Rødgaard-Hansen
authors.affiliation: Aarhus University Hospital, Department of Medicine V (Hepatology and Gastroenterology), Gastro-Immuno Research Laboratory (GIRL), Aarhus C, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Dige
authors.affiliation: Aarhus University Hospital, Department of Anaesthesiology and Intensive Care, Aarhus C, Denmark; Randers Regional Hospital, Department of Anaesthesiology and Intensive Care, Randers, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Krog
authors.affiliation: Aarhus University Hospital, Department of Clinical Biochemistry, Aarhus C, Denmark.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Aarhus University Hospital, Department of Anaesthesiology and Intensive Care, Aarhus C, Denmark.
authors.forename: Else
authors.initials: E
authors.lastname: Tønnesen
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000378:metabolism*; D002470:Cell Survival; D016638:Critical Illness; D003710:Demography; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D037181:Lectins, C-Type / Q000097:blood / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism*; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D012995:Solubility; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface