Serum and Tissue FGL2 as a Surrogate for Treg Cells Activity in Patients with Chronic Viral Hepatitis C (HCV)
OA Adeyi, N Selzner, I Shalev, Y Zhu, GA Levy. University of Toronto/UHN, Toronto, ON, Canada
Background: CD4+/CD25+/FoxP3+ T cells (Tregs) a subset of T cells have been implicated in the suppression of specific T cell-mediated immune responses to HCV. Tregs activity appears to correlate with more aggressive disease in HCV infected patients, suggesting that identification of these cells in serum and tissue could be an important prognostic marker. Hitherto FoxP3 was thought to be the most specific marker for Tregs, but recent data has cast doubts on their specificity. Data genearted in our lab our from mice studies supports the hypothesis that Fibrinogen-like protein (FGL2)/fibroleukin is an important effector molecule of Tregs. We have therefore tested the hypothesis that measurement of FGL2 as surrogate marker for Tregs activity in serum and liver tissue has prognostic value in predicting disease severity and response to antiviral therapy.
Design: We measured serum levels of human FGL2 using a highly sensitive and reproducible ELISA method in healthy individuals (controls) and post-transplant HCV- patients. The latter were grouped according to HCV genotype and response to antiviral therapy, to determine whether levels of FGL2 can be a useful prognostic marker of response to IFN therapy. FGL2 and FGL2/FoxP3 double staining was performed on randomly selected liver explants of these HCV patients.
Results: Serum levels of FGL2 were significantly higher in HCV patients (13.1+4.7ng/ml) than control (5.8+1.3 ng/ml p=0.007). HCV genotype 1 infected patients had higher levels of FGL2 (13.11+2.4ng/ml) than genotype 2/3 patients (6.1+1.4ng/ml) (p=0.04). Serum FGL2 levels were lower in patients who responded to anti-viral therapy than non-responders (3.5+1 ng/ml p =0.001) and was similar to non infected controls. FgL2 immunostaining demonstrated more positive cells among portal and lobular infiltrates in HCV patients with genotype 1 >> other genotypes. FoxP3/FGL2 co-staining showed that the majority of FoxP3+cells were not FGL2 positive, supporting the views that not all FoxP3+ cells are Tregs.
Conclusions: In HCV patients high Serum FGL2 levels, as surrogate for Tregs activity, mirror histopathologic findings and both correlate with known risk factors for progression (HCV genotype 1 and poor response to IFN). Serum and/or histologic demonstration of FGL2 could provide useful prognostic information in the management of HCV-infected patients. We have an ongoing prospective study to investigate the predictive value of serum and tissue FGL2 in HCV infection.
Category: Liver & Pancreas
Monday, March 9, 2009 1:15 PM
Platform Session: Section E, Monday Afternoon