Kinetic Study of Granzyme B in Patients with Chronic Hepatitis Type B

摘要

Chronic hepatitis B (CHB) virus infection is affecting more than 350 million people worldwide, and can predispose for serious complications like liver cirrhosis and hepatocarcinoma. The development of CHB from active stage is the direct result of debilitated immune system which mainly depends on cytotoxic T- lymphocyte (CTL) and natural killer (NK) cells for controlling viral replication. These cells eliminate their targets through the secretion of two proteins: perforin and granzymes (Gzms). Thus, this study aimed to evaluate the activity and concentration of GzmB in patients with CHB. A total of 60 patients (30 newly diagnosed and 30 treated) were recruited for this case-control study. Other 30 age- and gender-matched apparently healthy subjected (negative for HBsAg) were involved as controls. Granzyme B kinetics and concentration were measured using ready commercial kits. Treated patients had significantly higher values of Km (8.57±0.796 × 10~(-5) M), than either untreated patients (7.17±0.69 × 10~(-5) M) or controls (7.24±0.82 × 10~(-5) M), while treated patients showed significantly lower values for Kcat and Kcat/Km (3.77±0.39 s~(-1) and 4.55×0.89 × 10~4 M~(-1). s~(-1) respectively) than either untreated patients (4.37±0.31 s~(-1) and 6.18±0.98 × 10~4 M~(-1). s~(-1) respectively) or controls (4.34±0.37 s~(-1) and 6.187±1.167 × 10~4 M~(-1). s~(-1) respectively). Mean GzmB concentration in control was 104.4±26.37 Pg/mL which significantly higher than that of untreated patients (44.3±8.73. Pg/mL which did not differ significantly from treated patients (42.33±9.09 Pg/mL). These data indicate the reduction in GzmB concentration in CHB which may reflect a defect in the production of this enzyme that predispose un individual to the chronic infection.