The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection.
OBJECTIVE
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.
Foerster
Katharina
K
Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada.
Helmy
Ahmed
A
Zhu
Yi
Y
Khattar
Ramzi
R
Adeyi
Oyedele A
OA
Wong
Kit Man
KM
Shalev
Itay
I
Clark
David A
DA
Wong
Pui-Yuen
PY
Heathcote
Elizabeth J
EJ
Phillips
Melville J
MJ
Grant
David R
DR
Renner
Eberhard L
EL
Levy
Gary A
GA
Selzner
Nazia
N
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; C095202:FGL2 protein, human; D005340:Fibrinogen