| 研究実績の概要 |
Interstitial lung disease (ILD) can be classified into idiopathic pulmonary fibrosis (IPF) and non-IPF-ILD from a therapeutic perspective, but differential diagnosis between IPF and non-IPF-ILD can be difficult. The applicants hypothesized that proteins secreted from myofibroblasts could serve as useful serum biomarkers for distinguishing between IPF and non-IPF-ILD. They compared the gene profiling of myofibroblasts and normal lung fibroblasts in a mouse bleomycin-induced pulmonary fibrosis (IPF-like model). As a result, the gene expression of 10 secreted proteins was significantly increased in myofibroblasts of mouse lung fibrosis. Based on these results, the aim of this study is to identify multiple serum biomarkers useful for distinguishing between IPF and non-IPF-ILD and to perform functional analysis of these proteins.
We targeted 50 IPF patients, 42 non-IPF-ILD patients, and 30 healthy controls (Hamamatsu University School of Medicine) and measured serum concentrations of three clinically used serum markers (KL6, Surfactant protein-D [SP-D], LDH) and GREM1. Serum GREM1 was significantly higher in IPF patients (average 14.4 ng/mL), followed by non-IPF-ILD patients (8.8 ng/mL), and healthy controls (1.6 ng/mL). The area under the ROC curve (AUC) for IPF versus non-IPF-ILDs was 0.759 (95% confidence interval: 0.661-0.857), which was superior to KL6, SP-D, and LDH. The sensitivity of GREM1 (cutoff: 10.4 ng/mL) was 72%, and the specificity was 69%. Furthermore, immunostaining revealed strong expression of GREM1 in lung myofibroblasts.
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