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

BackgroundThe 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).ObjectiveWe 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.MethodsTwenty-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.ResultsAt 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.ConclusionThe macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new biomarker of sepsis.

Utility of immune response-derived biomarkers in the differential diagnosis of inflammatory disorders

“…Similar to the pattern observed in viral-bacterial discrimination, an increase of CRP to some level may be observed both in noninfectious SIRS and sepsis, limiting the specificity of low concentrations. Furthermore, some studies are limited by their methodological design: inclusion of patients with SIRS without the suspicion of an infection, 16,17,49 rather than the inclusion of consecutive patients from a clinical relevant population. 50e52 PCT has a better diagnostic accuracy than CRP for dicriminating infection from disease flare in febrile patients with a variety of auto-immune diseases.…”

“…91 Although these findings seem promising for the qualification of sMMR as a fungal biomarker, a recent small study in the ICU found sMMR concentrations to be elevated in patients with non-infectious SIRS (trauma and intracranial hemorrhage) and as well as bacterial sepsis. 49 …”

Diagnostic usefulness of sCD163, procalcitonin and neopterin for sepsis risk assessment in critically ill patients

“…In this study we also demonstrated statistically significant differences between the concentrations of sCD163 in the study group (patients with sepsis) and the reference group (patients without sepsis, in severe condition), but the AUC (0.847), sensitivity and specificity was lower than in the Kjaergaard et al publication. 25 Abdelrahman et al likewise analyzed the concentrations of sCD163 in ICU patients, which were divided into a study group (patients with sepsis) and a reference group (patients with SIRS). Based on the results obtained, the authors checked the diagnostic value of sCD163 in the diagnosis of sepsis and in the assessment of its severity.…”

Macrophage activation marker, soluble CD163, is an independent predictor of short‐term mortality in patients with cirrhosis and bacterial infection

“…Increased serum sCD163 level were found in non‐cirrhotic patients during bacterial infection and even higher levels in sepsis. An association between increased sCD163 level and reduced survival has also been reported . In cirrhosis, increased sCD163 level was reported in patients with significant portal hypertension or advanced disease stage .…”