背景:学龄前哮喘是哮喘发展的危险因素。然而,喘息发作背后的分子机制尚不清楚。
目的:我们的目的是评估血浆蛋白与急性学龄前喘息的相关性,并研究3个月后再次就诊时急性期差异表达的蛋白。此外,探讨蛋白表达与临床参数的关系。
方法:我们测量了145名儿童在学龄前喘息(PW)发作期间和3个月后再次就诊时的血浆和临床参数中的92种炎性蛋白(PW-R,n=113/145)和101个健康对照(HC)年龄6-48个月的GEWAC队列使用抗体介导的邻近延伸为基础的测定(Olink蛋白质组学,乌普萨拉)。
结果:在分析的74种蛋白质中,52在PW和HC之间差异表达。前10种蛋白质的表达谱,制瘤素M(OSM),IL-10,IL-6,成纤维细胞生长因子21(FGF21),AXIN1,CXCL10,SIRT2,TNFSF11,肿瘤坏死因子β(TNF-β)和CASP8几乎可以将PW与HC完全分开。10种蛋白质中有5种与采血前24小时口服皮质类固醇(OCS)的摄入量有关(OSM,CASP8、IL-10、TNF-β和CXCL10)。与HC相比,在有或没有OCS的PWs之间没有观察到蛋白质表达的差异。在三个月后的重访中,对于10种蛋白质中的3种(IL-10,SIRT2和FGF21),在PW-R和HC之间仍然观察到差异的蛋白质表达。
结论:我们的研究结果有助于揭示学龄前哮喘和哮喘之间潜在的免疫病理学途径。
BACKGROUND: Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.
OBJECTIVE: Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters.
METHODS: We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW-R, n = 113/145) and 101 healthy controls (HC) aged 6-48 months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala).
RESULTS: Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins.
CONCLUSIONS: Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.