The novel immunoregulatory molecule FGL2: A potential biomarker for severity of chronic hepatitis C virus infection

Katharina Foerster, Ahmed Helmy, Yi Zhu, Ramzi Khattar, Oyedele A. Adeyi, Kit Man Wong, Itay Shalev, David A. Clark, Pui Yuen Wong, Elizabeth J. Heathcote, Melville J. Phillips, David R. Grant, Eberhard L. Renner, Gary A. Levy, Nazia Selzner

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background & Aims: This report describes the use of a novel sensitive and specific ELISA for the measurement of human fibrinogen-like protein 2 (FGL2/fibroleukin), a novel effector of natural regulatory T (Treg) cells, to predict the course of chronic hepatitis C viral infection (HCV). Methods: Plasma levels of FGL2 were measured in HCV patients and compared to healthy controls and to patients with alcoholic liver disease. Results: FGL2 levels were significantly higher in HCV patients (84.3 ± 89.1 ng/ml, n = 80) compared to healthy controls (36.4 ± 21.9 ng/ml, n = 30, p <0.001), to a subset of patients who cleared HCV following anti-viral treatment (16.6 ± 19.7 ng/ml, n = 32, p <0.001), and to patients with inactive alcoholic liver disease (18.8 ± 17.4 ng/ml, n = 24, p <0.001). Among HCV patients, plasma levels of FGL2 correlated significantly with the stage of fibrosis (p = 0.001) and were significantly higher in patients with cirrhosis (164.1 + 121.8 ng/ml, n = 60) compared to non-cirrhotics (57.7 ± 52.8 ng/ml, n = 20, p = 0.001). Genotype 1 patients had significantly higher levels of FGL2 (98.1 ± 100.3 ng/ml, n = 60) compared to patients with genotype 2/3 (41.5 ± 38.6 ng/ml, n = 20, p = 0.0008). Patients with genotype 2/3 had FGL2 levels similar to healthy controls (41.5 ± 38.6 vs. 36.41 ± 21.9 ng/ml, p = ns). Infiltrating lymphocytes in liver biopsies of HCV patients were positive for either FGL2 or FoxP3 (a marker of Treg cells) or expressed both markers. Conclusions: This report documents the development of a sensitive ELISA for measurement of plasma levels of FGL2 an effector Treg cells, which correlates with the severity of HCV infection.

Original languageEnglish (US)
Pages (from-to)608-615
Number of pages8
JournalJournal of Hepatology
Volume53
Issue number4
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by a grant from The Physicians’ Services Incorporated Foundation (PSI). The authors have no potential conflicts to disclose.

Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.

Keywords

  • FGL2
  • HCV
  • Treg cells

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