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Biomark Insights. 2012; 7: 119–126.
Published online Sep 13, 2012. doi:  10.4137/BMI.S9415
PMCID: PMC3448496
Serological Investigation of the Collagen Degradation Profile of Patients with Chronic Obstructive Pulmonary Disease or Idiopathic Pulmonary Fibrosis
Diana J. Leeming,1 Jannie M. Sand,1 Mette J. Nielsen,1 Federica Genovese,1 Fernando J. Martinez,2 Cory M. Hogaboam,2 MeiLan K Han,2 Lloyd B. Klickstein,3 and Morten A. Karsdal1
1Nordic Bioscience A/S, Herlev, Denmark.
2Division of Pulmonary and Critical Care Medicine and Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
3Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Corresponding author email: djl/at/nordicbioscience.com
Abstract
In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-degraded type III collagen were assessed in serum of patients diagnosed with mild COPD (n = 10) or IPF (n = 30), and healthy controls (n = 15). The collagen degradation markers C1M, C3M, C5M and C6M were significantly elevated in serum of both mild COPD and IPF patients, versus controls. C3A and C4M were only elevated in patients with mild COPD, compared with controls. The most reliable indicators of mild COPD versus controls were: C1M (area under the receiver-operating characteristics (AUROC = 0.94, P < 0.0001), C3M (AUROC = 0.95, P < 0.0001), and C5M (AUROC = 0.95, P < 0.0001). The most reliable markers for the diagnosis of IPF were achieved by C1M (AUROC = 0.90, P < 0.0001) and C3M (AUROC = 0.93, P < 0.0001). Collagen degradation was highly up-regulated in patients with IPF and mild COPD, indicating that degradation fragments of collagens are potential markers of pulmonary diseases. Interestingly, C4M and C3A were only elevated in patients with mild COPD, indicating that these markers could be used to distinguish between the two pathologies.
Keywords: collagen, extracellular matrix remodeling, biochemical marker, neoepitope, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, matrix metalloproteinases
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