Holmdahl Idun, Chakraborty Sandip, Hoyer Angela, Filiou Anastasia, Asarnoj Anna, Sjölander Anders, Borres Magnus P, van Hage Marianne, Hedlin Gunilla, Konradsen Jon R, Söderhäll Cilla
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Clin Transl Allergy. 2023 Nov;13(11):e12308. doi: 10.1002/clt2.12308.
Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.
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.
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).
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.
Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.
学龄前喘息是哮喘发生的一个危险因素。然而，喘息发作背后的分子机制尚未完全明确。
我们旨在评估血浆蛋白与学龄前急性喘息的关联，并研究3个月后复诊急性期差异表达的蛋白。此外，探讨蛋白表达与临床参数之间的关系。
我们使用基于抗体介导的邻近延伸分析（瑞典乌普萨拉的Olink蛋白质组学公司），对GEWAC队列中145名6至48个月大的儿童在学龄前喘息发作期（PW）、3个月后复诊时（PW-R，n = 113/145）以及101名健康对照（HC）的血浆中的92种炎症蛋白和临床参数进行了测量。
在分析的74种蛋白中，有52种在PW和HC之间存在差异表达。排名前十的蛋白，即抑瘤素M（OSM）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）、成纤维细胞生长因子21（FGF21）、轴抑制蛋白1（AXIN1）、CXC趋化因子配体10（CXCL10）、沉默调节蛋白2（SIRT2）、肿瘤坏死因子配体超家族成员11（TNFSF11）、肿瘤坏死因子β（TNF-β）和半胱天冬酶8（CASP8）的表达谱几乎可以将PW与HC完全区分开来。10种蛋白中有5种与采血前24小时口服糖皮质激素（OCS）的摄入有关（OSM、CASP8、IL-10、TNF-β和CXCL10）。与HC相比，使用或未使用OCS的PW之间在蛋白表达上没有差异。在3个月后的复诊时，10种蛋白中的3种（IL-10、SIRT2和FGF21）在PW-R和HC之间仍存在差异蛋白表达。
我们的结果有助于揭示学龄前喘息和哮喘之间潜在的免疫病理途径。
