Taken together, these preliminary results indicate that the level of sFGL2 may be a useful biomarker of disease progression and response to therapy in patients with HCV infection. Figure 3. Mean plasma levels of sFGL2 in patients with chronic HCV infection. Ten (10) mL of heparinized blood was collected from 80 patients with chronic HCV infection, who had not received anti-viral therapy. Mean plasma levels of sFGL2 in these patients were … Preliminary Inhibitors,research,lifescience,medical data also demonstrated a significant difference in plasma levels of sFGL2 between HCV patients with genotype 1 compared to genotype 2/3 patients (120 versus 45 ng/mL).

The data to date suggest that patients with high levels of plasma sFGL2 (>150 ng/mL) have a more vigorous form of HCV with a higher probability of being non-responders to anti-viral therapy, whereas patients with levels <100 ng/mL are more likely to respond to anti-viral treatment. This is demonstrated in Figure 4, which shows the time-course

of sFGL2 levels in two representative patients with chronic HCV infection treated with Inhibitors,research,lifescience,medical anti-viral Inhibitors,research,lifescience,medical therapy. Patient 1 did not respond to 48 weeks of therapy with pegylated interferon and ribavirin. Plasma sFGL2 levels in patient 1 were very high prior to initiation of therapy, >300 ng/mL, and remained high throughout treatment and at 6 months post-treatment. In contrast, patient 2 had sFGL2 levels of less than 100 ng/mL prior to initiation of treatment; the level Inhibitors,research,lifescience,medical of sFGL2 fell within 4 weeks of therapy to levels seen in healthy controls, and levels of sFGL2 remained very low after completion of therapy. Figure 4. Time course of sFGL2 levels in two patients with chronic HCV infection treated with anti-viral therapy. A) Patient 1 with Inhibitors,research,lifescience,medical genotype 1 infection did

not respond to 48 weeks of therapy with pegylated interferon and Ribavirin. Plasma sFGL2 levels in this … We now also have preliminary pathological evidence for the interplay between Treg cells and FGL2 in patients with HCV infection. Figure 5 shows the co-expression of FGL2 (membrane and cytoplasmic) and Foxp3 (nuclear), the master transcription factor of Treg cells, in some of the inflammatory cells in the liver of a patient with chronic HCV infection. Figure 5. Pathological GBA3 evidence for the interplay between Treg cells and FGL2 in patients with HCV infection. Figure shows Vemurafenib mw immunohistochemistry staining of FGL2 (brown = membrane and cytoplasmic) and Foxp3 (blue = nuclear) in an explanted liver from an HCV patient. … In a preliminary study, we found that patients with high levels of FGL2 in the explanted liver are much more likely to have rapid and aggressive recurrence of HCV that responds poorly to treatment. Examples of the differences in the degree of FGL2 expression in the explanted liver of two patients and the correlation with the post-transplant clinical course are illustrated in Figure 6.