Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.
CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Allergy. 2019 Mar;74(3):507-517. doi: 10.1111/all.13570. Epub 2018 Oct 11.
Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker.
MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next-generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed.
We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR-185-5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR-185-5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma.
Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.
哮喘是一种以气道炎症和阻塞为特征的综合征。由于其异质性,哮喘的诊断和治疗困难使得新的生物标志物的发现成为研究的焦点。因此,我们确定了健康人和哮喘患者外周血嗜酸性粒细胞中差异表达的 miRNA,并建立了可在血清中检测到的差异表达 miRNA 谱,作为生物标志物。
通过下一代测序分离和分析来自健康和哮喘患者外周血嗜酸性粒细胞的 microRNA,并在 29 名哮喘患者和 10 名健康个体中通过定量 PCR 进行验证。在 138 名哮喘患者和 39 名健康个体中通过定量 PCR 检测血清中 miRNA 的水平。进行回归分析和随机森林模型分析。
我们发现了一组在哮喘患者和健康受试者的嗜酸性粒细胞中表达不同的 miRNAs。这些 miRNAs 可以将哮喘患者分为两个簇,在血清中嗜酸性粒细胞和periostin 浓度方面存在差异。其中一些 miRNAs 也在血清中得到了证实,例如 miR-185-5p 可以区分哮喘患者和健康受试者。miR-185-5p 与另外两个 miRNAs 一起,可以创建一个逻辑回归模型来更好地区分两种情况,以及一个随机森林模型,甚至可以将哮喘患者分为间歇性、轻度持续性、中度持续性和重度持续性哮喘。
我们的数据表明,嗜酸性粒细胞中的 miRNA 谱可以作为血清中哮喘诊断的生物标志物,并且该谱能够对哮喘严重程度进行分级。