Vázquez-Mera Sara, Martelo-Vidal Laura, Miguéns-Suárez Pablo, Saavedra-Nieves Paula, Arias Pilar, González-Fernández Coral, Mosteiro-Añón Mar, Corbacho-Abelaira María Dolores, Blanco-Aparicio Marina, Méndez-Brea Paula, Salgado Francisco Javier, Nieto-Fontarigo Juan José, González-Barcala Francisco Javier
Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Allergy. 2023 Jan;78(1):141-155. doi: 10.1111/all.15480. Epub 2022 Aug 29.
Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients.
Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2 -Atopic/T2 -Non-atopic/T2 ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR.
We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2 -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6 patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p.
Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.
哮喘是一种具有多种表型、内型和严重程度的异质性疾病，其中涉及不同的T细胞亚群。这些细胞表达特定的微小RNA（即炎症微小RNA），激活后可在外泌体中释放到血清中，并用作潜在炎症的生物标志物。因此，我们旨在评估哮喘患者不同亚组血清外泌体中的特定T细胞微小RNA特征。
使用来自健康供体（N = 30）和具有不同哮喘内型（T2 -特应性/T2 -非特应性/T2 ）和严重程度（轻度/轻度哮喘和中度-重度/中重度哮喘）的患者（N = 119）的样本。收集人口统计学、临床、血液学和生化特征。预先选择了12种先前与不同Th亚群相关的微小RNA，并使用RTqPCR测量其在血清外泌体样本中的水平。
我们在血清外泌体中高度可靠地检测到5种微小RNA：miR-16-5p、miR-21-5p、miR-126-3p、miR146a-5p和miR-215-5p。与轻度哮喘患者相比，中重度哮喘患者中除miR-16-5p外的所有这些微小RNA均上调。创建了一个包含每种这些微小RNA的逻辑回归模型来区分这两种情况，得出的ROC曲线AUC为0.896（0.830-0.961）。参与Th1/Th2分化的miR-21-5p和miR-126-3p在T2 -特应性患者中特异性增加。值得注意的是，所有这些变化都在秋季采集的样本中发现。相反，中重度哮喘患者中更肥胖、年龄更大、中性粒细胞和嗜碱性粒细胞计数及TNF水平更高的IL-6患者，其miR-21-5p、miR-126-3p和miR-146a-5p水平降低。
包括miR-21-5p、miR-126-3p、miR-146a-5p和miR-215-5p在内的免疫相关微小RNA可作为哮喘表型/内型和严重程度的临床相关非侵入性生物标志物。
