High plasma concentrations of osteopontin in patients with interstitial pneumonia

Abstract

Osteopontin (OPN) produced by alveolar macrophages functions as a fibrogenic cytokine in the development of bleomycin (BLM)-induced murine pulmonary fibrosis, and OPN mRNA is expressed on lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The present study investigates plasma OPN levels in human interstitial pneumonia (IP) and their relationships with disease severity by analyzing the correlation between plasma OPN concentrations and pulmonary functions. The concentrations of OPN in plasma were measured in 17 patients with IP, in 9 with sarcoidosis and in 20 healthy controls using an antigen-capture enzyme-linked immunosorbent assay. The concentrations of OPN in plasma were significantly higher in IP patients than in those with sarcoidosis or in controls. Based on a Receiver Operating Characteristic curve analysis, cut-off points between 300 and 380 ng/ml discriminated between IP and control subjects with 100% sensitivity and 100% specificity. In such case, the sensitivity for sarcoidosis decreased (55.5-33.3%) in cut-offs with 100% specificity. Plasma OPN levels inversely and closely correlated with arterial oxygen tension (PaO2) in patients with IP. Immunohistochemically, OPN was localized predominantly in macrophages and airway epithelium. These findings suggest that plasma OPN levels were found to be associated with the presence of IP, and that OPN play an important role in the development of IP.

Molecular biomarkers in idiopathic pulmonary fibrosis

“…OPN is elevated in the BALF and plasma of IPF patients compared with healthy controls, but plasma levels are not significantly different from other ILDs (36,67). In a mix of ILD including IPF, plasma OPN levels correlated with oxygenation but not pulmonary function parameters (36). OPN gene expression is increased in the lung tissue of IPF patients with progressive disease compared with those with stable disease (11).…”

“…OPN induces upregulation of MMP7 in AECs and colocalizes with MMP7 in AECs of IPF lungs (67). OPN is elevated in the BALF and plasma of IPF patients compared with healthy controls, but plasma levels are not significantly different from other ILDs (36,67). In a mix of ILD including IPF, plasma OPN levels correlated with oxygenation but not pulmonary function parameters (36).…”

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

“…Its role in promoting the migration, adhesion, and proliferation of fibroblasts has been demonstrated in a mouse model of bleomycininduced pulmonary fibrosis (29). A study in 2005 (30) found that levels of osteopontin in plasma were significantly higher in patients with ILDs than in those and SP-D had a worse 3-year survival rate.…”

Idiopathic pulmonary fibrosis biomarkers: clinical utility and a way of understanding disease pathogenesis

“…39 A small study of 17 ILD patients and nine patients with sarcoidosis found significantly elevated levels of serum OPN in both conditions compared to controls; there was also a significant difference found between ILD and sarcoidosis patients, although IPF patients were statistically indistinguishable from other ILD conditions. 40 This study noted an inverse correlation with arterial partial pressure of oxygen (PaO 2 ) levels but not with pulmonary function test (PFT) values. There was no significant correlation between OPN and other biomarkers, including KL-6 and SP-A and SP-D. 40 Despite the above discoveries strongly supporting a role for OPN in the pathogenesis of IPF, the data are insufficient to support its use as a biomarker for IPF.…”

“…40 This study noted an inverse correlation with arterial partial pressure of oxygen (PaO 2 ) levels but not with pulmonary function test (PFT) values. There was no significant correlation between OPN and other biomarkers, including KL-6 and SP-A and SP-D. 40 Despite the above discoveries strongly supporting a role for OPN in the pathogenesis of IPF, the data are insufficient to support its use as a biomarker for IPF.…”