Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex

Abstract

SummaryMannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBLassociated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0·003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.

Evaluation of the cytokine mannose-binding lectin as a mediator of periportal fibrosis progression in patients with schistosomiasis

“…Hepatic fibrosis depends on the actions of cytokines including mannose-binding lectin (MBL), which has a central regulatory role (5) . The association between the immune response of MBL and the development of hepatic fi brosis in other liver diseases has been evaluated (5) .…”

“…The association between the immune response of MBL and the development of hepatic fi brosis in other liver diseases has been evaluated (5) . The importance of MBL in the innate immune system is related to its multimeric structure as well as its functions as an opsonin and adaptor for the activation of mannose-binding lectin/mannose-binding protein-associated serine protease (MBL/MASPs).…”

“…The importance of MBL in the innate immune system is related to its multimeric structure as well as its functions as an opsonin and adaptor for the activation of mannose-binding lectin/mannose-binding protein-associated serine protease (MBL/MASPs). Moreover, the MBL serum level and enzyme activity of MBL/MASP-1 complex are elevated in hepatitis C virus (HCV) patients with severe hepatic fi brosis (5) . However, the contribution of MBL in patients with varying severity of S. mansoni remains poorly understood (6) .…”

“…The relationship between MBL and hepatic fi brosis in other hepatic diseases remains controversial (5) . The present study evaluated the infl uences of serum MBL level, age, sex, alcohol, exposure, and treatment on PPF severity in schistosomiasis.…”

“…Brown et al (5) investigated the infl uence of MBL level in patients with chronic HCV infection, non-HCV liver disease, and healthy controls from the Trent HCV cohort study in the UK (14) (15) ; they analyzed 147 infected patients and 111 healthy controls, and found MBL levels were signifi cantly higher in HCV patients with severe fi brosis than that in patients with mild fi brosis and controls. However, MBL levels did not differ signifi cantly between HCV and non-HCV liver disease patients.…”