Associations of circulating matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases with clinically relevant outcomes in idiopathic pulmonary fibrosis: Data from the IPF-PRO Registry

PLoS One. 2024 Oct 17;19(10):e0312044. doi: 10.1371/journal.pone.0312044. eCollection 2024.

Abstract

Introduction: We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry.

Methods: MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant).

Results: Over a median follow-up of 30.4 months, 98 patients died and 182 patients had disease progression. In unadjusted analyses, higher concentrations of MMPs 2, 3, 8 and 9 and TIMPs 1, 2 and 4 were associated with an increased risk of death. MMPs 2 and 8 and TIMP1 remained associated with death after adjustment for clinical factors. In unadjusted analyses, higher concentrations of MMPs 8 and 9 and TIMPs 1 and 4 were associated with an increased risk of disease progression. MMPs 8 and 9 and TIMP1 remained associated with progression after adjustment for clinical factors.

Conclusion: Circulating levels of MMP8 and TIMP1 may provide information on the risk of outcomes in patients with IPF not captured by clinical measures.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Disease Progression*
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis* / blood
  • Idiopathic Pulmonary Fibrosis* / mortality
  • Male
  • Matrix Metalloproteinases* / blood
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Registries*
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinases* / blood

Substances

  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases
  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-1
  • TIMP1 protein, human