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

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J Hepatol. 2010 Jun 17. [Epub ahead of print]

The novel immunoregulatory molecule FGL2: A potential biomarker for severity of

chronic hepatitis C virus infection.

Foerester K, Helmy A, Zhu Y, Khattar R, Adeyi OA, Wong KM, Shalev I, DA,

Wong PY, Heathcote EJ, MJ, Grant DR, Renner EL, Levy GA, Selzner N.

Multi Organ Transplant Program, University Health Network, University of

Toronto, Toronto, Canada.

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+/-89.1ng/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.

. Published by Elsevier B.V.

PMID: 20615566

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