MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease.Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF.In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4.MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

Diagnostic Accuracy of Serum Matrix Metalloproteinase‐7 for Biliary Atresia

“…Furthermore, serum MMP‐7 was also tested in healthy subjects of other age groups, including 6 months to 2 years and adults aged 25‐54 years old, which showed no substantial age‐based changes. Previous publications reported similar concentration ranges in normal subjects . Based on these findings, the trend observed in our analysis that MMP‐7 correlates with increasing age in BA and non‐BA subjects suggests that the increase may relate to the duration or severity of biliary injury.…”

“…Previous publications reported similar concentration ranges in normal subjects. (17,18) Based on these findings, the trend observed in our analysis that MMP-7 correlates with increasing age in BA and non-BA subjects suggests that the increase may relate to the duration or severity of biliary injury. However, these possibilities require further testing in future studies with larger cohort sizes in each age group.…”

The natural history of progressive fibrosing interstitial lung diseases

“…These include Krebs von den Lungen-6 protein (KL-6), which has been associated with a higher rate of disease progression in patients with IPF and CTD-ILDs [82][83][84][85], and surfactant protein-D (SP-D) [86,87]. Several studies have shown that levels of matrix metalloproteinase-7 (MMP-7), an enzyme involved in remodeling of the extracellular matrix, are negatively correlated with lung function and survival in patients with IPF [88][89][90][91]. Protein fragments generated by breakdown of the extracellular matrix have also been investigated as predictors of disease progression [92,93].…”

The interstitial lung disease multidisciplinary meeting: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia

“…Its recognition is significant given the impact of these disorders on post‐transplant outcomes . Diagnostic and prognostic efficacy of a vast array of specific biomarkers including Krebs von der Lungen 6 (KL6), surfactant proteins A and D and matrix metalloproteinases (MMP) 7 and 1 are being evaluated in IPF but are not currently part of routine clinical practice …”