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

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.