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MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis

Rosas, IO and Richards, TJ and Konishi, K and Zhang, Y and Gibson, K and Lokshin, AE and Lindell, KO and Cisneros, J and MacDonald, SD and Pardo, A and Sciurba, F and Dauber, J and Selman, M and Gochuico, BR and Kaminski, N (2008) MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Medicine, 5 (4). 0623 - 0633. ISSN 1549-1277

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Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression. Methods and Findings: We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins - MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A - that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%-100%) and specificity of 98.1% (95% CI 89.9%-100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%-100%) and specificity of 87.2% (95% CI 72.6%-95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%). Conclusions: Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases. Additionally, increased MMP7 concentration may be indicative of asymptomatic ILD and reflect disease progression.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rosas, IO
Richards, TJ
Konishi, K
Zhang, Yzhang3@pitt.eduZHANG3
Gibson, Kkfg@pitt.eduKFG
Lokshin, AE
Lindell, KOkol2@pitt.eduKOL2
Cisneros, J
MacDonald, SD
Pardo, A
Sciurba, Ffcs@pitt.eduFCS
Dauber, Jjimd@pitt.eduJIMD
Selman, M
Gochuico, BR
Kaminski, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBarnes, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 April 2008
Date Type: Publication
Journal or Publication Title: PLoS Medicine
Volume: 5
Number: 4
Page Range: 0623 - 0633
DOI or Unique Handle: 10.1371/journal.pmed.0050093
Refereed: Yes
ISSN: 1549-1277
PubMed ID: 18447576
Date Deposited: 18 Jul 2012 20:47
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/12954

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