| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2012;4(4):403-414
Original Article
Circulating levels of citrullinated and MMP-degraded vimentin (VICM)
in liver fibrosis related pathology
Efstathios Vassiliadis, Claudia P Oliveira, Mario R Alvares-da-Silva, Chen Zhang, Flair J Carrilho, Jose T Stefano,
Fabiola Rabelo, Leila Pereira, Camila R Kappel, Kim Henriksen, Sanne Skovgård Veidal, Ben Vainer, Kevin L
Duffin, Claus Christiansen, Diana J Leeming, Morten Karsdal
Assay Development, Nordic Bioscience, Copenhagen, Denmark; Department of Endocrinology, University of
Southern Denmark, Odense, Denmark; Technical University of Denmark, Department of Systems Biology, Lyngby,
Denmark; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Eli
Lilly and Company, Greenfield, Indiana, USA; University of São Paulo School of Medicine, Department of
Gastroenterology (LIM-07), São Paulo, SP, Brazil; Division of Gastroenterology, Hospital de Clinicas de Porto
Allegre, Univesidade Federal do Rio Grande do Sul, Porto Allegre, Brazil; 8Instituto do Figado de Pernambuco,
Pernambuco, Brazil
Received August 2, 2012; accepted September 16, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: Aim: 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 (CCl4) (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 CCl4-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). Conclusion: 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. (AJTR1208001).
Keywords: Biomarker, citrulline, hepatitis C, NAFLD
Address all correspondence to:
Dr. Efstathios Vassiliadis
Nordic Bioscience A/S, Herlev Hovedgade 207
DK-2730 Herlev, Denmark.
Tel: +45 44547738; Fax: +45 44525251
E-mail: eva@nordicbioscience.com
Original Article
Circulating levels of citrullinated and MMP-degraded vimentin (VICM)
in liver fibrosis related pathology
Efstathios Vassiliadis, Claudia P Oliveira, Mario R Alvares-da-Silva, Chen Zhang, Flair J Carrilho, Jose T Stefano,
Fabiola Rabelo, Leila Pereira, Camila R Kappel, Kim Henriksen, Sanne Skovgård Veidal, Ben Vainer, Kevin L
Duffin, Claus Christiansen, Diana J Leeming, Morten Karsdal
Assay Development, Nordic Bioscience, Copenhagen, Denmark; Department of Endocrinology, University of
Southern Denmark, Odense, Denmark; Technical University of Denmark, Department of Systems Biology, Lyngby,
Denmark; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Eli
Lilly and Company, Greenfield, Indiana, USA; University of São Paulo School of Medicine, Department of
Gastroenterology (LIM-07), São Paulo, SP, Brazil; Division of Gastroenterology, Hospital de Clinicas de Porto
Allegre, Univesidade Federal do Rio Grande do Sul, Porto Allegre, Brazil; 8Instituto do Figado de Pernambuco,
Pernambuco, Brazil
Received August 2, 2012; accepted September 16, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: Aim: 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 (CCl4) (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 CCl4-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). Conclusion: 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. (AJTR1208001).
Keywords: Biomarker, citrulline, hepatitis C, NAFLD
Address all correspondence to:
Dr. Efstathios Vassiliadis
Nordic Bioscience A/S, Herlev Hovedgade 207
DK-2730 Herlev, Denmark.
Tel: +45 44547738; Fax: +45 44525251
E-mail: eva@nordicbioscience.com
 | |  | |  | |  | |  | |  | |  |