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

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

doi:10.1016/j.jhep.2010.04.020

« Previous Next »Journal of Hepatology
Volume 53, Issue 4 , Pages 608-615, October 2010

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

Katharina Foerster
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Ahmed Helmy
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Yi Zhu
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Ramzi Khattar
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Oyedele A. Adeyi
- Department of Pathology, University of Toronto, Toronto, Canada
Kit Man Wong
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Itay Shalev
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
David A. Clark
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
- McMaster University, Hamilton, Canada
Pui-Yuen Wong
- Department of Biochemistry, University of Toronto, Toronto, Canada
Elizabeth J. Heathcote
- Department of Medicine, University of Toronto, Toronto, Canada
Melville J. Phillips
- Department of Pathology, University of Toronto, Toronto, Canada
David R. Grant
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Eberhard L. Renner
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
Gary A. Levy
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
- Corresponding author. Address: Multi Organ Transplant Program, University Health Network, Toronto General Hospital, NCSB 11-1236, 585 University Avenue, Toronto, ON, Canada M5G 2N2. Tel.: +1 (416) 340 5166; fax: +1 (416) 340 3378.
Nazia Selzner
- Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada

Received 23 September 2009; received in revised form 8 April 2010; accepted 12 April 2010. published online 24 June 2010.

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±89.1ng/ml, n=80) compared to healthy controls (36.4±21.9ng/ml, n=30, p<0.001), to a subset of patients who cleared HCV following anti-viral treatment (16.6±19.7ng/ml, n=32, p<0.001), and to patients with inactive alcoholic liver disease (18.8±17.4ng/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+121.8ng/ml, n=60) compared to non-cirrhotics (57.7±52.8ng/ml, n=20, p=0.001). Genotype 1 patients had significantly higher levels of FGL2 (98.1±100.3ng/ml, n=60) compared to patients with genotype 2/3 (41.5±38.6ng/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±21.9ng/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.

Abbreviations: DC, dendritic cells, FGL2, fibrinogen-like protein 2, HBV, hepatitis B virus, HCV, hepatitis C virus, MHV-3, murine hepatitis virus strain 3, SVR, sustained virological response, Treg, CD4⁺CD25⁺ regulatory T cells