Ishikawa Nobuhisa, Hattori Noboru, Yokoyama Akihito, Kohno Nobuoki
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Respir Investig. 2012 Mar;50(1):3-13. doi: 10.1016/j.resinv.2012.02.001. Epub 2012 Mar 8.
Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. Because injury and/or regeneration of type II pneumocytes are prominent histological features of ILDs, substances derived from type II pneumocytes have been the focus of research investigating potential biomarkers for ILD. One important biomarker for ILD is the high-molecular-weight glycoprotein, Krebs von den Lungen-6 (KL-6). KL-6 is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. KL-6/MUC1 is detectable in the serum of patients with ILD, and extensive investigations performed primarily in Japan have revealed that serum KL-6/MUC1 is elevated in 70-100% of patients with various ILDs, including idiopathic interstitial pneumonias, collagen vascular disease-associated interstitial pneumonia, hypersensitivity pneumonia, radiation pneumonitis, drug-induced ILDs, acute respiratory distress syndrome, pulmonary sarcoidosis, and pulmonary alveolar proteinosis. The results from these various studies have supported the utility of KL-6/MUC1 as a serum biomarker for detecting these various ILDs. Moreover, KL-6/MUC1 serum levels have been demonstrated to be useful for evaluating disease activity and predicting the clinical outcomes of various ILD types. Based on these observations, we believe that KL-6/MUC1 is currently one of the best and most reliable serum biomarkers available for ILD management.
间质性肺疾病(ILDs)是一组多样的肺部疾病,其特征是肺间质存在各种炎症和纤维化模式。由于II型肺泡上皮细胞的损伤和/或再生是ILDs突出的组织学特征,来自II型肺泡上皮细胞的物质一直是研究ILD潜在生物标志物的重点。ILD的一个重要生物标志物是高分子量糖蛋白克雷布斯-冯-登-伦根-6(KL-6)。KL-6现在被归类为人MUC1粘蛋白,再生的II型肺泡上皮细胞是ILD患者受影响肺部KL-6/MUC1的主要细胞来源。在ILD患者的血清中可检测到KL-6/MUC1,主要在日本进行的广泛研究表明,在包括特发性间质性肺炎、胶原血管病相关间质性肺炎、过敏性肺炎、放射性肺炎、药物性ILDs、急性呼吸窘迫综合征、肺结节病和肺泡蛋白沉积症在内的各种ILD患者中,70%-100%的患者血清KL-6/MUC1升高。这些不同研究的结果支持了KL-6/MUC1作为检测这些各种ILDs血清生物标志物的实用性。此外,KL-6/MUC1血清水平已被证明可用于评估疾病活动度和预测各种ILD类型的临床结局。基于这些观察结果,我们认为KL-6/MUC1目前是可用于ILD管理的最佳和最可靠的血清生物标志物之一。