Naftali Kaminski and colleagues find increased levels of specific proteins in the bloodstream of individuals with idiopathic pulmonary fibrosis, and suggest that these proteins may ultimately provide a biomarker for the disease

Anna E Lokshin

Annie Pardo

Bernadette R Gochuico

Bustos

Churg

Cosgrove

Costabel

Frank Sciurba

Fukuda

Gadek

Gibson

Gorelik

Greene

Ihaka

Ivan O Rosas

James Dauber

Jose Cisneros

Kadota

Kaminski

Kathleen O Lindell

Katzenstein

Kazuhisa Konishi

Keane

Kevin Gibson

King

Kuwano

McGuire

Moises Selman

Mukae

Naftali Kaminski

Novershtern

Ohtani

Pardo

Pauwels

Perez-Padilla

Peter Barnes

Rosas

Sandra D MacDonald

Selman

Silva

Steele

Suga

Thomas J Richards

Tusher

Vuorinen

Yang

Yingze Zhang

Yokoyama

PLoS Medicine

English

PubMed

Background:\ud
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.\ud
\ud
Methods and Findings:\ud
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\ud
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\ud
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%).\ud
\ud
Conclusions:\ud
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\ud
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

Rosas, Ivan O.

Richards, Thomas J.

Konishi, Kazuhisa

Zhang, Yingze

Gibson, Kevin

Lokshin, Anna E.

Lindell, Kathleen O.

Cisneros, Jose

MacDonald, Sandra D.

Pardo, Annie

Sciurba, Frank

Dauber, James

Selman, Moises

Gochuico, Bernadette R.

Kaminski, Naftali

Name not available

MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

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.%).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

Rosas Ivan O

Richards Thomas J

Konishi Kazuhisa

Zhang Yingze

Gibson Kevin

Lokshin Anna E

Lindell Kathleen O

Cisneros Jose

MacDonald Sandra D

Pardo Annie

Sciurba Frank

Dauber James

Selman Moises

Gochuico Bernadette R

Kaminski Naftali

Public Library of Science (PLOS)

Crossref

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

Rosas, IO

Richards, TJ

Konishi, K

Zhang, Y

Gibson, K

Lokshin, AE

Lindell, KO

Cisneros, J

MacDonald, SD

Pardo, A

Sciurba, F

Dauber, J

Selman, M

Gochuico, BR

Kaminski, N

D-Scholarship@Pitt

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

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.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%).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

Sandra D Macdonald

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http://d-scholarship.pitt.edu/12954/1/MMP1.pdf

MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

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Directory of Open Access Journals