He Daniel, Shannon Casey P, Hirota Jeremy A, Ask Kjetil, Ryerson Christopher J, Tebbutt Scott J
Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
PLoS One. 2024 Dec 3;19(12):e0314876. doi: 10.1371/journal.pone.0314876. eCollection 2024.
Fibrotic interstitial lung diseases (ILDs) result from excessive deposition of extracellular matrix (ECM) proteins in the lung, causing irreversible damage to the lung architecture. Clinical management of ILDs differs depending on the diagnosis, but differentiation between subtypes can be difficult and better clinical biomarkers are needed. In this study, we use a 166-gene NanoString assay to investigate whether there are ILD subtype-specific transcripts in whole blood. We identified one transcript, killer cell lectin like receptor 1 (KLRF1), as differentially expressed between idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated ILD (SSc-ILD), and identified two transcripts (VCAN, LTK) associated with IPF expression against other ILD subtypes. These findings were validated by examining their expression in ILD lung, with KLRF1 expression significantly higher in SSc-ILD compared to IPF and hypersensitivity pneumonitis (HP) samples. Taken together, this pilot study provides support for the use of the peripheral transcriptome in identifying diagnostic biomarkers of ILD with biological relevance.
纤维化间质性肺疾病（ILDs）是由细胞外基质（ECM）蛋白在肺中过度沉积所致，会对肺结构造成不可逆损害。ILDs的临床管理因诊断而异，但区分亚型可能存在困难，因此需要更好的临床生物标志物。在本研究中，我们使用一种166基因的NanoString检测法来研究全血中是否存在ILD亚型特异性转录本。我们鉴定出一种转录本，即杀伤细胞凝集素样受体1（KLRF1），在特发性肺纤维化（IPF）和系统性硬化症相关ILD（SSc-ILD）之间存在差异表达，并鉴定出两种与IPF表达相关的转录本（VCAN、LTK），相对于其他ILD亚型。通过检测它们在ILD肺中的表达对这些发现进行了验证，与IPF和过敏性肺炎（HP）样本相比，KLRF1在SSc-ILD中的表达显著更高。综上所述，这项初步研究为利用外周转录组来鉴定具有生物学相关性的ILD诊断生物标志物提供了支持。
