title: Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology.
abstract: OBJECTIVE
  To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.
  
  
  METHODS
  A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls.
  
  
  RESULTS
  In CCl(4)-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in F0 (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in F0 (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05).
  
  
  CONCLUSIONS
  We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.
authors.affiliation: Assay Development, Nordic Bioscience Copenhagen, Denmark ; Department of Endocrinology, University of Southern Denmark Odense, Denmark.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Vassiliadis
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Oliveira
authors.forename: Mario R
authors.initials: MR
authors.lastname: Alvares-da-Silva
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Flair J
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Jose T
authors.initials: JT
authors.lastname: Stefano
authors.forename: Fabiola
authors.initials: F
authors.lastname: Rabelo
authors.forename: Leila
authors.initials: L
authors.lastname: Pereira
authors.forename: Camila R
authors.initials: CR
authors.lastname: Kappel
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.forename: Sanne Skovgård
authors.initials: SS
authors.lastname: Veidal
authors.forename: Ben
authors.initials: B
authors.lastname: Vainer
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Duffin
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Morten
authors.initials: M
authors.lastname: Karsdal
keywords: Biomarker; NAFLD; citrulline; hepatitis C