title: 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: Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated 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.
authors.affiliation: Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
authors.forename: K S
authors.initials: KS
authors.lastname: Brown
authors.forename: M J
authors.initials: MJ
authors.lastname: Keogh
authors.forename: N
authors.initials: N
authors.lastname: Tagiuri
authors.forename: M J
authors.initials: MJ
authors.lastname: Grainge
authors.forename: J S
authors.initials: JS
authors.lastname: Presanis
authors.forename: S D
authors.initials: SD
authors.lastname: Ryder
authors.forename: W L
authors.initials: WL
authors.lastname: Irving
authors.forename: J K
authors.initials: JK
authors.lastname: Ball
authors.forename: R B
authors.initials: RB
authors.lastname: Sim
authors.forename: T P
authors.initials: TP
authors.lastname: Hickling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D037582:Complement Pathway, Mannose-Binding Lectin; D015986:Confounding Factors, Epidemiologic; D005234:Fatty Liver / Q000276:immunology / Q000473:pathology; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis*; D008875:Middle Aged
chemical_list: D037601:Mannose-Binding Lectin; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases