title: Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders.
abstract: OBJECTIVE
  Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer.
  
  
  METHODS
  Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls.
  
  
  RESULTS
  The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls.
  
  
  CONCLUSIONS
  MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark; The Technical University of Denmark, Department of Systems Biology, Kgs. Lyngby, Denmark. Electronic address: jhk@nordicbioscience.com.
authors.forename: J H
authors.initials: JH
authors.lastname: Kristensen
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Larsen
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dasgupta
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brodmerkel
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Curran
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: J M B
authors.initials: JM
authors.lastname: Sand
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Willumsen
authors.affiliation: Division of Respiratory Medicine and Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Knox
authors.affiliation: Division of Respiratory Medicine and Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: C E
authors.initials: CE
authors.lastname: Bolton
authors.affiliation: Division of Respiratory Medicine and Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: S R
authors.initials: SR
authors.lastname: Johnson
authors.affiliation: The Technical University of Denmark, Department of Systems Biology, Kgs. Lyngby, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Hägglund
authors.affiliation: The Technical University of Denmark, Department of Systems Biology, Kgs. Lyngby, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Svensson
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: D J
authors.initials: DJ
authors.lastname: Leeming
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000097:blood* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D059748:Proteolysis
chemical_list: D004549:Elastin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: Elastin; Idiopathic pulmonary fibrosis; Immunology; Lung carcinoma; Matrilysin; Metalloproteinases; Pulmonology