title: Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation.
abstract: BACKGROUND
  Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases.
  
  
  METHODS
  Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11).
  
  
  RESULTS
  The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06-280] for COPD and 50 [2.64-934] for IPF.
  
  
  CONCLUSIONS
  MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings.
authors: Nordic Bioscience A/S, DK-2730, Herlev, Denmark. HBE@nordicbioscience.com
authors: Helene
authors: H
authors: Skjøt-Arkil
authors: Rikke E
authors: RE
authors: Clausen
authors: Quoc Hai Trieu
authors: QH
authors: Nguyen
authors: Yaguo
authors: Y
authors: Wang
authors: Qinlong
authors: Q
authors: Zheng
authors: Fernando J
authors: FJ
authors: Martinez
authors: Cory M
authors: CM
authors: Hogaboam
authors: Meilan
authors: M
authors: Han
authors: Lloyd B
authors: LB
authors: Klickstein
authors: Martin R
authors: MR
authors: Larsen
authors: Arkadiusz
authors: A
authors: Nawrocki
authors: Diana J
authors: DJ
authors: Leeming
authors: Morten A
authors: MA
authors: Karsdal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004549:Elastin / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D000939:Epitopes / Q000097:blood; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000175:diagnosis*; D066298:In Vitro Techniques; D053508:Matrix Metalloproteinase 12 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000939:Epitopes; D004549:Elastin; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12