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Updated: Mar 9, 2026
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Type I interferon signaling in systemic immune cells from patients with alcoholic cirrhosis and its association with
Emmanuel Weiss1, Pierre-Emmanuel Rautou2, Magali Fasseu3
1INSERM, U1149, Centre de Recherche sur l'Inflammation (CRI), Clichy and Paris, France; UMR S_1149, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence Inflamex, ComUE Sorbonne Paris Cité, Paris, France; Département d'Anesthésie et Réanimation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
Background & Aims:
In immune cells, constitutively and acutely produced type I interferons (IFNs) engage autocrine/paracrine signaling pathways to induce IFN-stimulated genes (ISGs). Enhanced activity of IFN signaling pathways can cause excessive inflammation and tissue damage. We aimed to investigate ISG expression in systemic immune cells from patients with decompensated alcoholic cirrhosis, and its association with outcome.
Methods:
Peripheral blood mononuclear cells (PBMCs) from patients and heathy subjects were stimulated or not with lipopolysaccharide (LPS, an IFN inducer) or increasing concentrations of IFN-β. The expression of 48 ISGs and ten "non-ISG" inflammatory cytokines were analyzed using RT-qPCR.
Results:
We developed an 8-ISG signature (IFN score) assessing ISG expression. LPS-stimulated ISG induction was significantly lower in PBMCs from patients with cirrhosis compared to healthy controls. Non-ISGs, however, showed higher induction. Lower induction of ISGs by LPS was not due to decreased IFN production by cirrhotic PBMCs or neutralization of secreted IFN, but a defective PBMC response to IFN. This defect was at least in part due to decreased constitutive ISG expression. Patients with the higher baseline IFN scores and ISG levels had the higher risk of death. At baseline, "non-ISG" cytokines did not correlate with outcome.
Conclusions:
PBMCs from patients with decompensated alcoholic cirrhosis exhibit downregulated ISG expression, both constitutively and after an acute stimulus. Our finding that higher baseline PBMC ISG expression was associated with higher risk of death, suggests that constitutive ISG expression in systemic immune cells contributes to the prognosis of alcoholic cirrhosis.
Lay Summary:
Enhanced activity of IFN signaling pathways can cause excessive inflammation and tissue damage. Here we show that peripheral blood mononuclear cells (PBMCs) from patients with alcoholic cirrhosis exhibit a defect in interferon-stimulated genes (ISGs). We found that higher baseline ISG expression in PBMCs was associated with higher risk of death, revealing a probable contribution of ISG expression in immune cells to the outcome of alcoholic cirrhosis.
