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Updated: Oct 9, 2025
Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term
Johanna Reißing1, Philipp Lutz2,3, Mick Frissen1
1Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Background & Aims:
V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor modulating innate and adaptive immunity and affecting the resolution of bacterial infections. Given its expression on peritoneal macrophages (PMs), we hypothesised a prognostic role of peritoneal VSIG4 concentrations in patients with spontaneous bacterial peritonitis (SBP).
Methods:
We isolated PMs from patients with cirrhosis and analysed VSIG4 expression and release by flow cytometry, quantitative real-time PCR, ELISA, and confocal microscopy. We measured soluble VSIG4 concentrations in ascites from 120 patients with SBP and 40 patients without SBP and investigated the association of soluble VSIG4 in ascites with 90-day survival after SBP using Kaplan-Meier statistics, Cox regression, and competing-risks regression analysis.
Results:
VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK). VSIG4 gene expression in PMs decreased in patients with SBP and normalised after resolution. During SBP, VSIG4hi PMs were depleted (25% vs. 57%; p <0.001) and soluble VSIG4 in ascites were higher in patients with SBP than in patients without (0.73 vs. 0.35 μg/ml; p <0.0001). PM activation by Toll-like receptor (TLR) agonists or infection with live bacteria in vitro resulted in a loss of surface VSIG4 and the release of soluble VSIG4. Mechanistically, shedding of VSIG4 from PMs was protease-dependent and susceptible to microtubule transport inhibition. Soluble VSIG4 in ascites exceeded serum concentrations and correlated with serum creatinine, model for end-stage liver disease score and C-reactive protein during SBP. Concentrations of 1.0206 μg/ml or higher indicated increased 90-day mortality (hazard ratio 1.70; 95% CI 1.01-2.86; p = 0.046).
Conclusions:
VSIG4 is released from activated PMs into ascites during SBP. Higher peritoneal VSIG4 levels indicate patients with organ failure and poor prognosis.
Lay Summary:
Patients with liver cirrhosis who develop ascites have an increased risk of infection and mortality. Our study shows that in patients with infected ascites, the complement receptor VSIG4 is released by resident macrophages into the abdominal fluid where it can be measured. Patients with elevated levels of this protein in ascites are at high risk of dying within 90 days.
Insights
Elevated levels of V-set Ig-domain-containing 4 (VSIG4) in ascites indicate poor prognosis for patients with spontaneous bacterial peritonitis (SBP). Measuring peritoneal VSIG4 can help identify patients at high risk of mortality.
Area of Science:
- Immunology
- Hepatology
- Gastroenterology
Background:
- Patients with liver cirrhosis and ascites face heightened risks of infection and mortality.
- V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor involved in immune responses.
- VSIG4 is expressed on peritoneal macrophages (PMs), suggesting a potential role in spontaneous bacterial peritonitis (SBP).
Purpose of the Study:
- To investigate the prognostic role of VSIG4 concentrations in ascites of patients with SBP.
- To determine the relationship between VSIG4 expression on PMs and SBP.
- To explore the mechanism of VSIG4 release during SBP.
Main Methods:
- Isolation and analysis of PMs from cirrhotic patients using flow cytometry, qPCR, ELISA, and microscopy.
- Measurement of soluble VSIG4 in ascites from SBP patients and controls.
- Association analysis of ascites VSIG4 levels with 90-day survival using statistical models.
Main Results:
- VSIG4 expression was high on resting PMs but decreased during SBP, with increased soluble VSIG4 in ascites.
- PM activation led to VSIG4 shedding, a process dependent on proteases and microtubule transport.
- Elevated ascites VSIG4 levels correlated with disease severity markers and predicted increased 90-day mortality.
Conclusions:
- VSIG4 is released from activated PMs into the peritoneal fluid during SBP.
- Higher VSIG4 levels in ascites signify organ failure and a poor prognosis in SBP patients.
- Peritoneal VSIG4 serves as a valuable prognostic biomarker for SBP.
