KL-6, a Mucin-like Glycoprotein, in Bronchoalveolar Lavage Fluid from Patients with Interstitial Lung Disease

Abstract

KL-6, a mucin-like high-molecular-weight glycoprotein, is a serum marker indicating the disease activity of pneumonitis, such as idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and sarcoidosis. Immunohistochemical studies have shown that KL-6 is strongly expressed on Type 2 pneumocytes and also exists on epithelial cells in other organs. It has not been clarified whether the increased levels of KL-6 in sera from patients with pneumonitis are derived from the lower respiratory tract. In this study, KL-6 levels were evaluated in bronchoalveolar lavage fluid (BALF) samples from 9 healthy control subjects and 32 patients with interstitial pneumonitis. An abnormally high level of KL-6 in BALF was observed in 70% (7 of 10) of patients with IPF, 64% (9 of 14) of patients with sarcoidosis, and 100% (8 of 8) of patients with hypersensitivity pneumonitis but in none of the healthy control subjects. KL-6 levels in BALF were significantly correlated with numbers of total cells (p < 0.001), lymphocytes (p < 0.001), and neutrophils (p < 0.05) and with concentrations of albumin (p < 0.001) and total protein (p < 0.001) in BALF and, further, with serum KL-6 levels (p < 0.01). These results indicate that increased levels of serum KL-6 in patients with pneumonitis reflect the production levels of KL-6 derived from damaged or regenerating Type 2 pneumocytes in the lower respiratory tract.

Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

“…The high-molecular-weight pulmonary epithelial mucin KL-6 is an integral membrane glycoprotein that appears to be predominantly expressed on injured and/or activated alveolar type II cells (19). Recently, we reported that the localization of KL-6 protein appeared primarily on the apical surface of alveolar type II cells in postmortem ARDS patients (1).…”

“…This glycoprotein is mainly expressed on alveolar type II cells in the lung (20) and is expressed more prominently on proliferating, regenerating, or injured type II cells than on normal type II cells (19,20). The presence of KL-6 has been used to monitor severity of disease in idiopathic pulmonary fibrosis (19).…”

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

“…KL-6's value in diagnosing patients with ILDs compared to healthy controls has been demonstrated by several studies (8,9). The clinical cut-off value for distinguishing patients with ILDs from healthy subjects and patients with lung diseases other than ILDs had been set at the level of 500 U/mL (10).…”

“…Levels of KL-6 in BALF were reported to be consistent with those in serum (5,8,9), whereas the levels of SP-A and SP-D in BALF were reported to be inversely correlated with levels in serum (19)(20)(21). Although the levels of KL-6, SP-A and SP-D in BALF are potential biomarkers for IPF, the inconvenience of obtaining BALF has resulted in their limited use clinically.…”

KL-6 and Surfactant Proteins A and D in Serum and Bronchoalveolar Lavage Fluid in Patients with Acute Eosinophilic Pneumonia

“…Several studies have measured the levels of KL-6, SP-A, and SP-D in the bronchoalveolar lavage fluid (BALF) of IPF patients in attempt to understand how those levels become elevated (14)(15)(16). It has been thought that the destruction of the alveolar epithelium and endothelium might cause hyperlucent blood.…”