Wardzyńska Aleksandra, Pawełczyk Małgorzata, Rywaniak Joanna, Kurowski Marcin, Makowska Joanna S, Kowalski Marek L
Department of Immunology and Allergy, Medical University of Lodz, Lodz, Poland.
Department of Rheumatology, Medical University of Lodz, Lodz, Poland.
Allergy Asthma Immunol Res. 2020 Jan;12(1):125-136. doi: 10.4168/aair.2020.12.1.125.
Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations.
Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry.
Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO ( = 0.44, < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found.
Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.
哮喘加重的免疫机制尚未阐明。本研究旨在评估各种哮喘加重特征与选定血清微小RNA（miRNA）表达及T细胞亚群之间的关联。
对21例哮喘患者在哮喘加重期（加重期就诊[EV]及6周后的随访就诊[FV]）进行研究。在两次就诊时，均进行肺功能测定、测量呼出一氧化氮分数（FeNO），并采集鼻咽和血液样本。在鼻咽样本中，通过多重聚合酶链反应（PCR）检测呼吸道病毒，并进行细菌培养。采用实时PCR检测血清miRNA。通过流式细胞术评估T细胞表面标志物、嗜酸性粒细胞祖细胞和细胞内细胞因子。
三分之二的患者有中度或重度加重，在FV时，观察到哮喘控制总体改善。血清miRNA-126a、miRNA-16和miRNA-21的平均表达在EV时显著低于FV时。在EV时，miRNA-29b与FeNO相关（r = 0.44，P < 0.05），7种检测的miRNA中有5种与肺功能测试相关。分化簇（CD）45+CD4+白细胞介素（IL）4+细胞的数量在EV时显著高于FV时，且发现调节性T细胞和嗜酸性粒细胞祖细胞与哮喘控制呈正相关。在EV时，血清miRNA与表达IL-4、IL-17、IL-22和干扰素γ的T细胞数量呈负相关，而在FV时，观察到与T细胞亚群既有正相关又有负相关。未发现鼻咽液中检测到的病原体（病毒和细菌）与临床、功能和免疫参数之间存在关联。
哮喘加重期间的表观遗传失调可能与呼吸功能、气道炎症和T细胞细胞因子表达有关。
