title: Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease.
abstract: A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore the diagnostic features of neo-epitope fragments of type III collagen generated by cathepsins that could reflect the pathological tissue turnover in patients with different diseases. A novel enzyme-linked immunosorbent assay (ELISA) measuring cathepsins B, L, S and K -generated type III collagen fragments (C3C) was developed for assessment in serum and plasma. The assay was biologically validated in serum from patients with chronic obstructive pulmonary disease (COPD). Serological levels of C3C were significantly elevated in patients with COPD compared to healthy controls (p = 0.0006). Levels of C3C in serum and heparin plasma of COPD patients had a highly significant correlation (R2 = 0.86, p<0.0001). The data suggests that the C3C fragment is elevated in patients with COPD compared to healthy controls.
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.|University of Southern Denmark, Institute of Molecular Medicine, Cardiovascular and Renal Research, Institute of Clinical Research, Odense, Denmark.
authors.forename: Daniel Guldager Kring
authors.identifier: http://orcid.org/0000-0003-1642-7482
authors.initials: DG
authors.lastname: Rasmussen
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: Jannie Marie Bülow
authors.initials: JM
authors.lastname: Sand
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: Federica
authors.initials: F
authors.lastname: Genovese
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D016022:Case-Control Studies; D002403:Cathepsins / Q000378:metabolism*; D024061:Collagen Type III / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007164:Immunosorbents; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D059748:Proteolysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis*
chemical_list: D024061:Collagen Type III; D000939:Epitopes; D007164:Immunosorbents; D002403:Cathepsins