Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis

Abstract

YKL-40, a mammalian member of chitinase-like proteins, has been shown to play a role in pathological conditions leading to tissue remodeling and fibrosis. Recently, YKL-40 was found to be increased in severe asthma, suggesting that YKL-40 contributes to airway remodeling; however, no data are available about YKL-40 expression in idiopathic pulmonary fibrosis (IPF). The present study was conducted to investigate YKL-40 expression in the serum and lung of IPF patients, and to determine its clinical significance. Using an enzyme-linked immunosorbent assay, we measured YKL-40 levels in the serum of 63 IPF patients and in bronchoalveolar lavage fluid (BALF) of 18 IPF patients. YKL-40 levels were also assessed in the serum and BALF of healthy subjects. We further investigated the relationship between serum YKL-40 levels and clinical parameters. Additionally, immunohistochemical staining for YKL-40 was performed in lung specimens of IPF patients and control subjects. Serum and BALF YKL-40 levels were significantly higher in IPF than in controls (serum: 245.8+/-180.2ng/ml vs. 116.0+/-58.3ng/ml; BALF: 17.8+/-19.1ng/ml vs. 0.3+/-0.9ng/ml, respectively). Serum YKL-40 levels significantly correlated positively with serum KL-6 levels and AaDO(2), and negatively with DLco and PaO(2). Immunohistochemical study revealed enhanced YKL-40 expression in alveolar macrophages and bronchiolar epithelia adjacent to fibrotic lesions in IPF, but not in controls. These data suggest that YKL-40 is increased in the circulation and lungs of IPF patients, suggesting that this glycoprotein is associated with the pathophysiology of IPF.