Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality.
AF, ascitic fluid
BSA, bovine serum albumin
Bacterial infection
Biomarker
C3, complement component 3
CCR2, C-C chemokine receptor type 2
EEA1, early endosome antigen 1
FCS, foetal calf serum
FMO, fluorescence minus one
HLA-DR, human leucocyte antigen-DR isotype
IMC, isotype-matched control
INR, international normalised ratio
LAMP2, lysosome-associated membrane protein 2
LPS, lipopolysaccharide
MACS, magnet-activated cell sorting
MELD, model for end-stage liver disease
MERTK, tyrosine-protein kinase Mer
MFI, median fluorescence intensity
MMP, matrix metalloproteinase
MOI, multiplicity of infection
MPLA, monophosphoryl lipid A
PAMP, pathogen-associated molecular pattern
PD-L1, programmed cell death 1 ligand 1
PFA, paraformaldehyde
PM, peritoneal macrophage
Prognostic factor
Risk of death
SBP, spontaneous bacterial peritonitis
TAPI-2, tumour necrosis factor protease inhibitor 2
TLR, Toll-like receptor
TNF, tumour necrosis factor
VSIG4, V-set Ig-domain-containing 4
qRT-PCR, quantitative real-time PCR
sVSIG4, soluble V-set Ig-domain-containing 4
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
23
04
2021
revised:
01
10
2021
accepted:
20
10
2021
entrez:
17
12
2021
pubmed:
18
12
2021
medline:
18
12
2021
Statut:
epublish
Résumé
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). 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. VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK). VSIG4 is released from activated PMs into ascites during SBP. Higher peritoneal VSIG4 levels indicate patients with organ failure and poor prognosis. 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.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
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
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
RESULTS
VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK).
CONCLUSIONS
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
BACKGROUND
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.
Identifiants
pubmed: 34917912
doi: 10.1016/j.jhepr.2021.100391
pii: S2589-5559(21)00167-1
pmc: PMC8666561
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100391Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
All authors declare no conflict of interest with regard to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details.
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