PT - JOURNAL ARTICLE AU - Jacob Hull Kristensen AU - Bidisha Dasgupta AU - Jannie Marie Sand AU - Carrie Brodmerkel AU - Mark Curran AU - Morten Asser Karsdal AU - Diana Julie Leeming TI - Neutrophil elastase degraded elastin is elevated in serum of idiopathic pulmonary fibrosis DP - 2014 Sep 01 TA - European Respiratory Journal PG - P3915 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/P3915.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/P3915.full SO - Eur Respir J2014 Sep 01; 44 AB - Introduction: Elastin is a signature protein of the lungs and loss of elasticity is a pathological feature of Idiopathic pulmonary fibrosis (IPF). The pathogenesis involves tissue turnover mediated by proteases upregulated during disease, especially neutrophil elastase (NE).Aim: We developed an ELISA for the assessment of elastin degradation mediated by NE (EL-NE). The objective was to investigate the ability of this marker to non-invasively diagnose IPF.Methods: A NE generated elastin neoepitope was chosen for monoclonal antibody generation for development of the EL-NE marker for the assessment of elastin NE degradation in serological samples. Elastin purified from lung was degraded in vitro cleaved by NE and a number of other proteinases and measured by EL-NE. The technical robustness of EL-NE was also tested. Furthermore, EL-NE was assessed in baseline serum samples of 124 IPF patients from a prior phase 2 study (CTgov reg. NCT00786201) and in 19 healthy controls.Results: EL-NE was specific towards NE degraded lung elastin with three orders of magnitude compared to elastin degraded by other proteinases and intact elastin. The assay was found to be technical robust. EL-NE was significantly increased in IPF serum samples (p=0.010)) compared to healthy controls. Stratified for severity EL-NE could differentiate between mild (FVC≥ 80%) and moderate IPF (FVC 50-80%) with borderline significance (p=0.06).Conclusion: We developed a technical robust marker that is specific for NE degraded elastin. Serum NE-derived elastin fragments were significantly elevated in IPF patients thus EL-NE may be a potential marker of diagnosis and possibly progression in IPF patients.