Leeming Diana J, Sand Jannie M, Nielsen Mette J, Genovese Federica, Martinez Fernando J, Hogaboam Cory M, Han Meilan K, Klickstein Lloyd B, Karsdal Morten A
Nordic Bioscience A/S, Herlev, Denmark.
Biomark Insights. 2012;7:119-26. doi: 10.4137/BMI.S9415. Epub 2012 Sep 13.
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.
在慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)中,肺组织内均会出现异常高水平的胶原重塑。在被诊断为轻度COPD(n = 10)或IPF(n = 30)的患者以及健康对照者(n = 15)的血清中,评估了基质金属蛋白酶(MMP)降解的I、III、IV、V和VI型胶原以及含血小板反应蛋白基序的解聚素和金属蛋白酶(ADAMTS)降解的III型胶原。与对照组相比,轻度COPD和IPF患者血清中的胶原降解标志物C1M、C3M、C5M和C6M均显著升高。与对照组相比,C3A和C4M仅在轻度COPD患者中升高。轻度COPD与对照组相比最可靠的指标为:C1M(受试者工作特征曲线下面积(AUROC)= 0.94,P < 0.0001)、C3M(AUROC = 0.95,P < 0.0001)和C5M(AUROC = 0.95,P < 0.0001)。诊断IPF最可靠的标志物是C1M(AUROC = 0.90,P < 0.0001)和C3M(AUROC = 0.93,P < 0.0001)。IPF和轻度COPD患者的胶原降解高度上调,表明胶原降解片段是肺部疾病的潜在标志物。有趣的是,C4M和C3A仅在轻度COPD患者中升高,表明这些标志物可用于区分这两种病理情况。