Enríquez-Rodríguez Cesar Jessé, Casadevall Carme, Faner Rosa, Castro-Costa Ady, Pascual-Guàrdia Sergi, Seijó Luis, López-Campos José Luis, Peces-Barba Germán, Monsó Eduard, Barreiro Esther, Cosío Borja G, Agustí Alvar, Gea Joaquim
Servei de Pneumologia, Hospital del Mar - IMIM, MELIS Dept, Universitat Pompeu Fabra and BRN, Barcelona, Spain.
Centro de Investigación Biomédica en Red, Área de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
ERJ Open Res. 2024 Mar 25;10(2). doi: 10.1183/23120541.00004-2024. eCollection 2024 Mar.
Some patients with COPD suffer frequent exacerbations (FE). We hypothesised that their systemic proteomic profile would be different from that of non-frequent exacerbators (NFE). The objective of the present study was to contrast the systemic proteomic profile in FE NFE. As a reference, we also determined the systemic proteomic profile of healthy controls (HC) and COPD patients during an actual episode of exacerbation (AE).
In the analysis we included 40 clinically stable COPD patients (20 FE and 20 NFE), and 20 HC and 10 AE patients. Their plasma samples were analysed by combining two complementary proteomic approaches: label-free liquid chromatography-tandem mass spectrometry and multiplex immunoassays. Gene Ontology annotation, pathway enrichment and network analyses were used to investigate molecular pathways associated with differentially abundant proteins/peptides (DAPs).
Compared with HC, we identified 40 DAPs in FE, 10 in NFE and 63 in AE. Also compared to HC, pathway functional and protein-protein network analyses revealed dysregulation of inflammatory responses involving innate and antibody-mediated immunity in COPD, particularly in the FE group, as well as during an AE episode. Besides, we only identified alterations in the complement and coagulation cascades in AE.
There are specific plasma proteome profiles associated with FE, which are partially shared with findings observed during AE, albeit others are uniquely present during the actual episode of AE.
一些慢性阻塞性肺疾病（COPD）患者频繁急性加重（FE）。我们假设他们的全身蛋白质组谱将不同于非频繁急性加重者（NFE）。本研究的目的是对比FE和NFE的全身蛋白质组谱。作为对照，我们还测定了健康对照（HC）和处于急性加重期（AE）的COPD患者的全身蛋白质组谱。
在分析中，我们纳入了40例临床稳定的COPD患者（20例FE和20例NFE）、20例HC和10例AE患者。通过结合两种互补的蛋白质组学方法对他们的血浆样本进行分析：无标记液相色谱 - 串联质谱法和多重免疫测定法。使用基因本体注释、通路富集和网络分析来研究与差异丰富蛋白质/肽（DAP）相关的分子通路。
与HC相比，我们在FE中鉴定出40种DAP，在NFE中鉴定出10种，在AE中鉴定出63种。同样与HC相比，通路功能和蛋白质 - 蛋白质网络分析显示，COPD中涉及先天免疫和抗体介导免疫的炎症反应失调，特别是在FE组以及AE发作期间。此外，我们仅在AE中鉴定出补体和凝血级联反应的改变。
存在与FE相关的特定血浆蛋白质组谱，其中部分与AE期间观察到的结果相同，尽管其他部分仅在AE实际发作期间出现。
