A Promising Biomarker of Fibrogenesis in the Liver, TGF-beta LAP-D

TGF-beta the most potent fibrogenic cytokine, is secreted as a latent complex, in which TGF-beta is trapped by its pre-peptide, latency associated protein (LAP). We have been exploring if LAP degradates (LAP-D), generated during the activation of TGF-beta by plasma kallikrein via cleavage of LAP between R58 and L59, might reflect fibrogenesis at local sites. We made R58 and L59 mouse monoclonal antibodies that detect N- and C-terminal sides of LAP-D containing cutting edges of R58 and L59, respectively. Here, we explored promising utility of LAP-D as a novel marker reflecting hepatic fibrogenesis activity in patients. L59 LAP-D levels in plasma samples in 200 patients were measured by ELISA. There was no correlation between LAP-D and other biomarkers. More than ~25% of hepatitis patients, ranged as F0-2 stages in METAVIR score, exceeded the criteria range. Plasma LAP-D moved up and down in course of viral hepatitis. Even if plasma HBV-DNA inhibited by a nucleic acid analog treatment, plasma LAP-D increased in some cases. Six months after starting the PEG-interferon/ribavirin therapy in HCV patients, the plasma LAP-D levels decreased to the half of individual levels before starting the treatment. LAP-D would be novel markers in blood and tissues reflecting fibrogenesis activity and can be used to estimate early stage of fibrosis.