IL-18 binding protein can be a prognostic biomarker for idiopathic pulmonary fibrosis.
IL-18 binding protein can be a prognostic biomarker for idiopathic pulmonary fibrosis.
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DOI：
10.1371/journal.pone.0252594
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Hattori N
中科院分区：
文献类型：
--
作者：
Nakanishi Y;Horimasu Y;Yamaguchi K;Sakamoto S;Masuda T;Nakashima T;Miyamoto S;Iwamoto H;Ohshimo S;Fujitaka K;Hamada H;Hattori N
特发性肺纤维化是一种慢性间质性肺炎，表现为各种临床病程和进展，从快到慢不等。为了寻找能够支持特发性肺纤维化诊断和/或预后预测的新的生物标志物，我们进行了基因表达分析，与健康对照组相比，特发性肺纤维化患者白细胞介素18结合蛋白的mRNA表达增加。因此，我们假设白介素18结合蛋白可以作为特发性肺纤维化的诊断和/或预后的生物标志物。我们研究了IL-18结合蛋白在肺组织、支气管肺泡灌洗液和血清中的表达。此外，通过皮下注射博莱霉素诱导的小鼠肺纤维化模型，研究了白介素18结合蛋白表达水平与纤维化程度之间的相关性。特发性肺纤维化患者血清IL-18结合蛋白水平(5.06 ng/mL，四分位数范围：4.20-6.35)显著高于健康对照组(3.31 ng/mL，IQR：2.84-3.99)(p<；0.001)。多因素Logistic回归模型显示，在调整了年龄、性别和吸烟状况后，血清白介素18结合蛋白水平与特发性肺纤维化之间的相关性在统计学上是独立的。多变量COX比例风险模型显示，血清白介素18结合蛋白水平独立于其他协变量因素预测特发性肺纤维化的预后(风险比：1.655，95%可信区间：1.224-2.237，p=0.001)。博莱霉素组小鼠肺组织羟脯氨酸表达水平与肺泡灌洗液中白介素18结合蛋白水平呈显著正相关(Spearman r=0.509，p=0.004)。这些结果表明，白介素18结合蛋白可作为特发性肺纤维化的一种新的预后生物标志物。
Idiopathic pulmonary fibrosis is a chronic, fibrosing interstitial pneumonia that presents with various clinical courses and progression ranging from rapid to slow. To identify novel biomarkers that can support the diagnosis and/or prognostic prediction of idiopathic pulmonary fibrosis, we performed gene expression analysis, and the mRNA of interleukin-18 binding protein was increasingly expressed in patients with idiopathic pulmonary fibrosis compared with healthy controls. Therefore, we hypothesized that the interleukin-18 binding protein can serve as a diagnostic and/or prognostic biomarker for idiopathic pulmonary fibrosis. We investigated the expression of interleukin-18 binding protein in lung tissue, bronchoalveolar lavage fluid, and serum. Additionally, the correlation between interleukin-18 binding protein expression levels and the extent of fibrosis was investigated using mouse models of lung fibrosis induced by subcutaneous bleomycin injections. Serum interleukin-18 binding protein levels were significantly higher in idiopathic pulmonary fibrosis patients (5.06 ng/mL, interquartile range [IQR]: 4.20–6.35) than in healthy volunteers (3.31 ng/mL, IQR: 2.84–3.99) (p < 0.001). Multivariate logistic regression models revealed that the correlation between serum interleukin-18 binding protein levels and idiopathic pulmonary fibrosis was statistically independent after adjustment for age, sex, and smoking status. Multivariate Cox proportional hazard models revealed that serum interleukin-18 binding protein levels were predictive of idiopathic pulmonary fibrosis disease prognosis independent of other covariate factors (hazard ratio: 1.655, 95% confidence interval: 1.224–2.237, p = 0.001). We also demonstrated a significant positive correlation between lung hydroxyproline expression levels and interleukin-18 binding protein levels in bronchoalveolar lavage fluid from bleomycin-treated mice (Spearman r = 0.509, p = 0.004). These results indicate the utility of interleukin-18 binding protein as a novel prognostic biomarker for idiopathic pulmonary fibrosis.
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