Functional Proteomic Laboratory, Department of Life Sciences, University of Siena, Siena, Italy.
Respiratory Diseases and Lung Transplant Unit, Department of Internal and Specialist Medicine AOUS, University of Siena, Siena, Italy.
Rheumatology (Oxford). 2019 Jan 1;58(1):165-178. doi: 10.1093/rheumatology/key223.
SSc is a rare severe connective tissue disorder. Its prognosis is mainly related to the development of pulmonary fibrosis (PF)-SSc and pulmonary arterial hypertension. No known therapy for PF-SSc modifies progressive lung fibrotic involvement. Research is therefore aimed at a deeper understanding of complex pathogenetic mechanisms and the possibility of new prognostic biomarkers and therapeutic targets.
Towards the first of these aims, we conducted functional proteomic analysis of bronchoalveolar lavage samples from PF-SSc patients and smoker and non-smoker controls.
The differential expression pattern revealed by principal component analysis highlighted a specific protein profile of PF-SSc with respect to control samples, and enrichment analysis shed light on process networks involved in pathogenesis. The proteins identified are known to be involved in lung inflammation of PF-SSc-induced IL6 signalling, the complement system, innate immunity, Jak-STAT, the kallikrein-kinin system, blood coagulation, the immune response mediated by phagocytosis and phagosomes in antigen presentation. In particular, our MetaCore network suggested C3a, APOAI, 14-3-3ε, SPFA2 and S100A6 as potential biomarkers; these are upstream molecules involved in lung fibrosis, innate immunity and vascular damage occurring in PF-SSc.
This report provides a molecular overview of pathological processes in PF-SSc, pinpointing possible new disease biomarkers and therapeutic targets.
SSc 是一种罕见的严重结缔组织疾病。其预后主要与肺纤维化（PF）-SSc 和肺动脉高压的发展有关。目前尚无已知的治疗方法可改善 PF-SSc 的进行性肺纤维化。因此，研究旨在更深入地了解复杂的发病机制，并寻找新的预后生物标志物和治疗靶点。
为了实现第一个目标，我们对 PF-SSc 患者、吸烟者和非吸烟者对照者的支气管肺泡灌洗液样本进行了功能蛋白质组学分析。
主成分分析显示的差异表达模式突出了 PF-SSc 相对于对照样本的特定蛋白质谱，富集分析揭示了参与发病机制的过程网络。鉴定出的蛋白质已知参与 PF-SSc 诱导的 IL6 信号、补体系统、固有免疫、Jak-STAT、激肽释放酶-激肽系统、凝血、吞噬作用介导的免疫反应和抗原呈递中的吞噬体。特别是，我们的 MetaCore 网络提示 C3a、APOAI、14-3-3ε、SPFA2 和 S100A6 作为潜在的生物标志物；这些是参与 PF-SSc 中肺纤维化、固有免疫和血管损伤的上游分子。
本报告提供了 PF-SSc 病理过程的分子概述，指出了可能的新疾病生物标志物和治疗靶点。
