Suchankova Magda, Zsemlye Eszter, Urban Jan, Baráth Peter, Kohútová Lenka, Siváková Barbara, Ganovska Martina, Tibenska Elena, Szaboova Kinga, Tedlova Eva, Juskanic Dominik, Kluckova Kristina, Kardohelyova Michaela, Moskalets Tetiana, Ohradanova-Repic Anna, Babulic Patrik, Bucova Maria, Leksa Vladimir
Laboratory of Molecular Immunology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
Institute of Immunology, Faculty of Medicine Comenius University, Bratislava, Slovakia.
Front Immunol. 2025 Jan 13;15:1479458. doi: 10.3389/fimmu.2024.1479458. eCollection 2024.
Diffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition. The major hallmark of lung fibrosis is uncontrolled activation of lung fibroblasts to myofibroblasts associated with extracellular matrix deposition and the loss of both lung structure and function.
Here, we used this peculiar feature in order to identify specific biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluids (BALF). The primary MRC-5 human fibroblasts were activated with BALF collected from patients with clinically diagnosed lung fibrosis; the activated fibroblasts were then washed rigorously, and further incubated to allow secretion. Afterwards, the secretomes were analysed by mass spectrometry.
In this way, the protein was identified; consequently, BALF of all DPLD patients were positively tested for the presence of by ELISA. Finally, biochemical and biophysical characterizations revealed an exosomal origin of . Receiver operating characteristics curve analysis confirmed in BALF as a specific and reliable biomarker of IPF and other types of DPLD accompanied with pulmonary fibrosis.
弥漫性肺实质疾病（DPLD）涵盖多种不同类型的肺部疾病。在众多病理表型中，肺纤维化是最具破坏性的，是特发性肺纤维化（IPF）的特征性标志。尽管肺纤维化预后不佳，但对于这种致命疾病的初始发展，尚无特异性诊断生物标志物。肺纤维化的主要标志是肺成纤维细胞不受控制地激活为肌成纤维细胞，伴有细胞外基质沉积以及肺结构和功能的丧失。
在此，我们利用这一独特特征来鉴定支气管肺泡灌洗液（BALF）中肺纤维化的特异性生物标志物。用从临床诊断为肺纤维化患者收集的BALF激活原代MRC - 5人成纤维细胞；然后对激活的成纤维细胞进行严格洗涤，并进一步孵育以使其分泌。之后，通过质谱分析分泌蛋白组。
通过这种方式鉴定出了该蛋白质；因此，所有DPLD患者的BALF通过酶联免疫吸附测定法（ELISA）检测该蛋白质均呈阳性。最后，生化和生物物理特征表明该蛋白质起源于外泌体。受试者工作特征曲线分析证实BALF中的该蛋白质是IPF和其他伴有肺纤维化的DPLD类型的特异性且可靠的生物标志物。
