MMP7-degraded elastin is elevated in serum of patients with idiopathic pulmonary fibrosis

Introduction: Elastin is an abundant protein of the lung and is responsible for the elastic recoil following inflation. Idiopathic pulmonary fibrosis (IPF) causes altered elastin remodeling and fibrosis, which in part is believed to be mediated by MMP7, possibly resulting in the release of specific elastin fragments into the circulation. Aims: Our aims were to investigate whether MMP7 generated specific elastin peptides; and to develop a highly specific assay for the assessment of MMP7-degraded elastin in serum, and investigate its ability to describe IPF. Methods: A monoclonal antibody was raised against a MMP7 cleavage site in elastin and employed in an ELISA (ELM7). Technical robustness was tested and ELM7 levels were compared in intact elastin and elastin cleaved in vitro by MMP2, MMP7, MMP9, and neutrophil elastase (NE). ELM7 was assessed in baseline serum of 124 IPF patients from a prior phase 2 study (CTgov reg. [NCT00786201][1]) and in 19 healthy controls. Results: Technical data for the ELM7 were acceptable. ELM7 exclusively recognized MMP7-cleaved elastin with concentrations elevated up to 17-fold above intact elastin and elastin cleaved by MMP2, MMP9, or NE, to which almost no reactivity was seen. Serum ELM7 was significantly elevated in IPF patients compared to controls (23%, p = 0.0353), but no correlation to FVC was observed. Conclusion: MMP7 degradation of elastin resulted in unique protein fragments, which may be more disease specific than traditional elastin peptides. ELM7 was specific only towards MMP7-degraded elastin and was able to separate IPF patients from healthy controls. These preliminary results show a good potential for ELM7 as a marker of elastin remodeling during IPF. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00786201&atom=%2Ferj%2F44%2FSuppl_58%2FP823.atom