Article

Soluble CD163 from activated macrophages predicts mortality in acute liver failure

University of California, San Diego, San Diego, California, United States
Journal of Hepatology (Impact Factor: 10.4). 12/2007; 47(5):671-6. DOI: 10.1016/j.jhep.2007.05.014
Source: PubMed

ABSTRACT Soluble CD163 (sCD163) is a scavenger receptor shed in serum during inflammatory activation of macrophages. We investigated if sCD163 was increased and predicted outcome in acute liver failure (ALF).
Samples from 100 consecutive patients enrolled in the U.S. ALF Study Group for whom sera were available were collected on days 1 and 3, and clinical data were obtained prospectively. sCD163 levels were determined by ELISA.
The median level of sCD163 was significantly increased in ALF (21.1mg/l (range 3.6-74.9)) as compared to healthy controls (2.3mg/l (0.65-5.6), p<0.0001) and patients with stable liver cirrhosis (9.8mg/l (3.6-16.9), p=0.0002). sCD163 on day 1 correlated significantly with ALT, AST, bilirubin, and creatinine. sCD163 concentrations on day 3 were elevated in patients with fatal outcome of disease compared to spontaneous survivors, 29.0mg/l (7.2-54.0) vs. 14.6mg/l (3.5-67.2), respectively (p=0.0025). Patients that were transplanted had intermediate levels. Sensitivity and specificity at a cut-off level of 26mg/l was 62% and 81%, respectively.
Activated macrophages are involved in ALF resulting in a 10-fold increase in sCD163. A high level (>26mg/l) of sCD163 was significantly correlated with fatal outcome and might be used with other parameters to determine prognosis.

Download full-text

Full-text

Available from: Holger Jon Møller, Jun 30, 2015
0 Followers
 · 
110 Views
  • Source
    Journal of Hepatology 08/2014; 61(2). DOI:10.1016/j.jhep.2014.03.031 · 10.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND & AIMS: Soluble CD 163 (sCD163) is shed in the blood circulation by activated macrophages, correlates strongly with the hepatic venous pressure gradient (HVPG) and is thereby a good indicator for portal hypertension. It is unknown if sCD163 correlates with the risk of variceal bleeding and overall survival (OS) in patients with liver cirrhosis. We performed a prospective study to investigate if sCD163 serum levels correlate with the risk of variceal bleeding and with OS in cirrhotic patients. METHODS: Patients with liver cirrhosis were prospectively enrolled and followed until death or last contact. At the day of inclusion into the study blood samples were taken and the sCD163 serum levels were assessed by ELISA (Enzyme-linked immunosorbent assay). The time until the end points death and variceal bleeding were assessed and the risks of death or variceal bleeding were calculated with uni- and multivariate Cox regression analyses. RESULTS: High sCD163 levels (> 4100 ng/l) were associated with death independently from the MELD (model of end stage liver disease) score, CRP (C-reactive protein), age and gender. Furthermore, high sCD163 levels were associated with gastrointestinal bleeding independently from the variceal stage and red spots. CONCLUSIONS: The sCD163 serum level is a new independent non-invasive risk factor for death and variceal bleeding in cirrhotic patients.
    Journal of Hepatology 01/2013; 58(5). DOI:10.1016/j.jhep.2013.01.005 · 10.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scavenger receptor CD163 contains nine scavenger receptor cysteine-rich (SRCR) domains and because of the presence of this ancient and highly conserved protein motif, CD163 belongs to the SRCR superfamily. Expression of CD163 is restricted to cells of the monocyte/macrophage lineage and is tightly regulated, with a general tendency of anti-inflammatory signals to induce CD163 synthesis, while pro-inflammatory signals rather seem to downregulate CD163 expression. The first-identified and most-studied function of CD163 is related to its capacity to bind and internalize haemoglobin-haptoglobin (HbHp) complexes. Later on, its functional repertoire was expanded, with the identification of CD163 as an erythroblast adhesion receptor, a receptor for tumour necrosis factor-like weak inducer of apoptosis (TWEAK), as well as a receptor for distinct pathogens encompassing bacteria and viruses. Interaction of one of these ligands with CD163 might result in receptor-mediated endocytosis, but might as well trigger a signalling cascade leading to the secretion of signalling molecules, which implicates that CD163 also acts as an immunomodulator. Not only the membrane-bound form of CD163 has an immunomodulating capacity, but also soluble CD163, which is generated via ectodomain shedding, is able to exert anti-inflammatory effects. Furthermore, the concentration of this soluble protein is significantly increased under specific pathological conditions, making it a useful marker protein for certain diseases. Finally, its restricted expression pattern and potential to internalize make CD163 an attractive candidate as gateway for cell-directed (immuno)therapy. This review aims to summarize current knowledge on CD163's biology and its different biological functions beyond HbHp scavenging, thereby mainly focussing on the more recently discovered ones. Furthermore, current data supporting the capacity of CD163 to serve as a diagnostic marker in certain diseases and its potential as a target molecule for cell-directed therapy are surveyed.
    Molecular Immunology 03/2010; 47(7-8):1650-60. DOI:10.1016/j.molimm.2010.02.008 · 3.00 Impact Factor