Publication by Rosas IO, et al (PLoS Med. 2008;5(4):e93.)

Commentary by Charlie Strange, MD, of the Medical University of South Carolina

Article Summary

MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis.
Rosas IO, Richards TJ, Konishi K, et al. PLoS Med. 2008;5(4):e93.

Introduction:

High through-put analysis of cellular RNA levels is an important genomics tool and has been applied to IPF. However, RNA levels do not always reflect protein levels, and RNA profiling can be difficult to apply to proteins such as hormones or cytokines that are not synthesized at their site of action.

These investigators measured the plasma concentrations of 49 candidate proteins to discover whether there is a peripheral blood protein signature that is characteristic of IPF.

Methods:

  • The concentrations of 49 proteins were determined with a multianalyte protein assay system. In plasma from patients with IPF (N = 74), COPD (N = 73), sarcoidosis (N = 47), hypersensitivity pneumonitis (HP) (N = 41), and controls
    (N = 53)
  • After obtaining the results from the original group, a validation cohort of control patients (N = 20), patients with subclinical idiopathic ILD (N = 8), sporadic IPF (N = 9), and familial pulmonary fibrosis (N = 16) were studied for serum matrix metalloproteinase 1 (MMP1) and matrix metalloproteinase 7 (MMP7)
  • Open lung biopsies from IPF patients (N = 23) and controls (N = 14) were analyzed with oligonucleotide gene expression arrays to correlate peripheral proteins with gene expression in the lung tissue
  • Bronchoalveolar lavage (BAL) from 22 patients with IPF and 10 controls was analyzed for MMP1 and MMP7

Results:

  • Plasma levels of twelve proteins were found to be different between IPF and controls. MMP1 and MMP7 were elevated in the plasma of patients with IPF; levels of these proteins discriminate between patients with IPF and controls, as well as patients with COPD, HP, and sarcoidosis
  • MMP1 and MMP7 were overexpressed in IPF lung tissue and BAL fluid compared to controls
  • The combination of serum MMP1 and MMP7 had higher sensitivity and specificity than either marker alone
  • MMP7 levels correlate with disease severity and are significantly elevated in patients with subclinical interstitial lung disease (ILD)

Expert Opinion:

Blood markers that sensitively and specifically define IPF would be a great advance in pulmonary medicine. No longer would we need to subject elderly patients to the stress of an open lung biopsy. No longer would we mistake advanced chronic HP as IPF. Ideally, a profile of blood markers would give a definitive diagnosis of all ILDs.

The limitation of this paper is that both the original study cohort and the validation cohort are small and do not include important idiopathic interstitial pneumonias such as non-specific interstitial pneumonitis (NSIP) that have a markedly different clinical course than IPF.

Nevertheless, the description of MMP1 and MMP7 as serum and lung biomarkers (better used in combination than individually) brings us closer to developing better diagnostic tools for IPF. Further studies are necessary before this tool enters the mainstream of diagnostic pulmonary medicine.

Article Link

Rosas IO, Richards TJ, Konishi K, et al. MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med. 2008;5(4):e93.

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