Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Lung. 2021 Jun;199(3):289-298. doi: 10.1007/s00408-021-00440-y. Epub 2021 Mar 26.
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.
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.
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.
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.
间质性肺疾病（ILDs），特别是特发性肺纤维化（IPF）与其他非 IPFILDs 的鉴别诊断，对于选择合适的治疗方法很重要。本回顾性研究旨在探讨 Gremlin-1 在鉴别诊断中的作用。
采用 ELISA 法检测 50 例 IPF 患者、42 例非 IPFILD 患者和 30 例健康对照者的血清 Gremlin-1 浓度。通过病历回顾获取基线临床数据，包括肺功能、预后和三种血清标志物（KL6、SP-D 和 LDH），分析其与血清 Gremlin-1 浓度的关系。为了评估 Gremlin-1 的来源，我们对肺组织切片进行免疫染色。
IPF 患者的血清 Gremlin-1 浓度明显升高（平均浓度为 14.4ng/ml），其次是非 IPFILD 患者（8.8ng/ml）和健康对照组（1.6ng/ml）。IPF 与非 IPFILD 之间的曲线下面积为 0.759（95%置信区间，0.661-0.857），优于 KL6/SP-D/LDH。Gremlin-1（截断值 10.4ng/ml）的敏感性和特异性分别为 72%和 69%。相比之下，血清 Gremlin-1 浓度与所有 ILD 患者的肺功能或预后均无相关性。在免疫染色中，Gremlin-1 在 IPF 肺中广泛上调，特别是在肌成纤维细胞、细支气管/肺泡上皮和 CD163 阳性的 M2 样巨噬细胞中。
与非 IPFILD 相比，Gremlin-1 可能是一种提高 IPF 诊断准确性的有用生物标志物，提示该分子在 IPF 的发病机制中起作用。
