Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland.
Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Eur J Clin Invest. 2019 Sep;49(9):e13153. doi: 10.1111/eci.13153. Epub 2019 Jul 11.
Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the fibrotic changes in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular analysis of BALf cells from IPF and sarcoidosis patients.
Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real-time PCR in 32 samples (11 IPF and 21 sarcoidosis).
The number of genes differentially expressed between IPF and sarcoidosis groups was 4832 (13359 probesets). Cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis.
Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells. The most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.
结节病和特发性肺纤维化（IPF）是两种最常见的间质性肺疾病（ILDs）。支气管肺泡灌洗液（BALf）的细胞和生化成分被证明反映了肺部的纤维化变化。然而，BALf 细胞谱评估在ILDs 诊断中的有用性是有限的。本研究的目的是对 IPF 和结节病患者的 BALf 细胞进行多变量、分子分析。
使用 Affymetrix Human Gene 2.1 ST ArrayStrip 在 21 个样本中进行转录组测量：9 个 IPF 和 12 个结节病。通过实时 PCR 评估最显著区分基因的 mRNA 表达在 32 个样本（11 个 IPF 和 21 个结节病）中进行。
IPF 和结节病组之间差异表达的基因数量为 4832 个（13359 个探针）。聚类分析表明，结节病 BALf 细胞的特征是核糖体生物发生相关基因的 mRNA 表达增加。在 IPF 样本中改变 mRNA 表达的基因形成的聚类与细胞黏附与迁移、金属蛋白酶表达和细胞增殖的负调控过程有关。GO 分析表明，与 BALf 细胞差异 mRNA 基因表达相关的主要生物学过程是 IPF 中中性粒细胞的上调和结节病中淋巴细胞的上调。
对结节病和 IPF 的 BALf 分析显示细胞的 mRNA 谱高度不同。在 BALf 细胞中观察到的分子水平上最重要的生物学过程与结节病中的核糖体生物发生和蛋白酶体装置以及 IPF 中的中性粒细胞功能障碍有关。
