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

Katharina Foerester 1, Ahmed Helmy 1, Yi Zhu 1, Ramzi Khattar 1, Oyedele A. Adeyi 2, Kit Man Wong 1, Itay Shalev 1, David A. Clark 1 5, Pui-Yuen Wong 3, Elizabeth J. Heathcote 4, Melville J. Phillips 2, David R. Grant 1, Eberhard L. Renner 1, Gary A. Levy 1, Nazia Selzner 1

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

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

Keywords: FGL2, HCV, Treg cells

Source