Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland.
Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland.
J Allergy Clin Immunol. 2017 Nov;140(5):1288-1298. doi: 10.1016/j.jaci.2017.05.040. Epub 2017 Jun 19.
Seasonal allergic rhinitis (SAR) caused by intermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with profound effects on quality of life, work productivity, and school performance. Although both the genotype and environmental factors can contribute to the immunologic basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear.
To address these questions, nasal epithelial brushings were collected from 29 patients with SAR and 31 control subjects during and after the pollen season. We then implemented an orbitrap-based, bottom-up, label-free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant (DA) proteins among the 4 sample groups.
We identified a total of 133 DA proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, cystatin 1 and myeloblastin, the former of which protects against protease activity of allergens and the latter with a role in epithelial barrier function, were DA in patients with SAR and control subjects, irrespective of season. Moreover, interferon-inducible protein with tetratricopeptide repeats 1, cystatin 1, and interferon-inducible protein with tetratricopeptide repeats 3 were found to be differentially regulated between patients with SAR and control subjects, with inverse abundance dynamics during the transition from fall to spring.
We identified type 1 interferon-regulated proteins as biomarkers in patients with SAR, potentially playing an important role in its pathogenesis. Moreover, when compared with patients with SAR, healthy subjects exhibit an antagonistic proteomic response across seasons, which might prove to be a therapeutic target for disease prevention.
由季节性花粉间歇性暴露引起的季节性过敏性鼻炎(SAR)会导致瘙痒、鼻塞和反复打喷嚏,对生活质量、工作效率和学业成绩产生深远影响。尽管基因型和环境因素都可以促成过敏反应的免疫学基础,但与过敏性鼻炎发病机制相关的分子基础尚不完全清楚。
为了解决这些问题,我们在花粉季节期间和之后从 29 名 SAR 患者和 31 名对照者的鼻上皮刷中采集样本。然后,我们采用基于轨道阱的、自下而上的、无标记定量蛋白质组学方法,并进行多变量分析,以确定 4 个样本组中差异丰富(DA)的蛋白质。
我们共鉴定出 133 个 DA 蛋白,其中最显著的过度代表功能类别是干扰素 1 信号。两种蛋白质,半胱氨酸蛋白酶抑制剂 1 和髓过氧化物酶,前者可防止过敏原的蛋白酶活性,后者在上皮屏障功能中起作用,在 SAR 患者和对照者中均为 DA,而与季节无关。此外,干扰素诱导的四肽重复蛋白 1、半胱氨酸蛋白酶抑制剂 1 和干扰素诱导的四肽重复蛋白 3 在 SAR 患者和对照者之间存在差异调节,在从秋季到春季的转变过程中,其丰度动态相反。
我们鉴定出 1 型干扰素调节蛋白作为 SAR 患者的生物标志物,它们可能在其发病机制中发挥重要作用。此外,与 SAR 患者相比,健康受试者在整个季节表现出拮抗的蛋白质组反应,这可能成为疾病预防的治疗靶点。