Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases

Abstract

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.

Clinical characteristics of idiopathic pulmonary fibrosis patients according to their smoking status

“…On the other hand, dyspnea duration, KL-6, and HRCT emphysema score were strong predictors of AE in smoking IPF patients. Our laboratory findings of smoking IPF patients revealed a relatively high mean KL-6 value which may signify a greater risk for fibrosis (27)(28)(29).…”

Advances in the study of biomarkers of idiopathic pulmonary fibrosis in Japan

“…KL-6 has been used in clinical practice for more than 10 years in Japan, and KL-6 levels are examined in more than 2,000,000 samples per year in Japan (24). Kits to measure KL-6, SP-A, and SP-D have been successfully developed by reagent manufacturers (Picolumi KL-6: Sanko Junyaku Co., Tokyo, Japan; SP-A test-F: Kokusai Shiyaku Co., Hyogo, Japan; SP-D kit Yamasa; YamasaShoyu Co., Tokyo, Japan).…”

Interstitial Pneumonia Associated with Connective Tissue Disease: An Overview and an Insight

“…SP-D serum levels are more sensitive than SP-A in detecting ILD as defined by CT but less specific [23]. KL-6 is a high-molecular-weight mucinlike glycoprotein, now classified as MUC1, which is highly expressed by AEC II and bronchiolar epithelial cells and increases following cellular injury and/or regeneration [24]. KL-6 has profibrotic and antiapoptotic effects on lung fibroblasts [25].…”

“…Serum KL-6 has been shown to be elevated not only in IIP but also in CTD-ILD, as well as hypersensitivity pneumonitis, drug-induced pneumonitis, etc. [24,26].…”