Gremlin-1 for the Differential Diagnosis of Idiopathic Pulmonary Fibrosis Versus Other Interstitial Lung Diseases: A Clinical and Pathophysiological Analysis

被引:14
作者
Aoshima, Yoichiro [1 ,2 ]
Enomoto, Yasunori [1 ]
Muto, Shigeki [3 ]
Meguro, Shiori [1 ]
Kawasaki, Hideya [1 ]
Kosugi, Isao [1 ]
Fujisawa, Tomoyuki [2 ]
Enomoto, Noriyuki [2 ]
Inui, Naoki [2 ]
Nakamura, Yutaro [2 ]
Suda, Takafumi [2 ]
Iwashita, Toshihide [1 ]
机构
[1] Hamamatsu Univ Sch Med, Dept Regenerat & Infect Pathol, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[2] Hamamatsu Univ Sch Med, Dept Internal Med, Div 2, Hamamatsu, Shizuoka, Japan
[3] Seirei Ctr Hlth Promot & Prevent Med, Dept Hlth Care, Hamamatsu, Shizuoka, Japan
关键词
Gremlin-1; Interstitial lung disease; Idiopathic pulmonary fibrosis; Biomarker; Differential diagnosis;
D O I
10.1007/s00408-021-00440-y
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Purpose The differential diagnosis of interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF) versus other non-IPF ILDs, is important for selecting the appropriate treatment. This retrospective study aimed to explore the utility of gremlin-1 for the differential diagnosis. Methods Serum gremlin-1 concentrations were measured using an ELISA in 50 patients with IPF, 42 patients with non-IPF ILD, and 30 healthy controls. The baseline clinical data, including pulmonary functions, prognosis, and three serum biomarkers (Krebs von den Lungen-6 [KL6], surfactant protein-D [SP-D], and lactate dehydrogenase [LDH]), were obtained through a medical record review for analyzing their associations with serum gremlin-1 concentrations. To evaluate the origin of gremlin-1, we performed immunostaining on lung sections. Results Serum gremlin-1 concentrations were significantly higher in patients with IPF (mean concentration, 14.4 ng/mL), followed by those with non-IPF ILD (8.8 ng/mL) and healthy controls (1.6 ng/mL). The area under the curve for IPF versus non-IPF ILDs was 0.759 (95% confidence interval, 0.661-0.857), which was superior to that of KL6/SP-D/LDH. The sensitivity and specificity for gremlin-1 (cutoff, 10.4 ng/mL) was 72 and 69%, respectively. By contrast, serum gremlin-1 concentrations were not associated with the pulmonary functions nor the prognosis in all patients with ILDs. In immunostaining, the gremlin-1 was broadly upregulated in IPF lungs, particularly at myofibroblasts, bronchiolar/alveolar epithelium, and CD163-positive M2-like macrophages. Conclusions Gremlin-1 may be a useful biomarker to improve the diagnostic accuracy for IPF compared to non-IPF ILDs, suggesting a role of this molecule in the pathogenesis of IPF.
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收藏
页码:289 / 298
页数:10
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