Department of Allergy, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Institute of Genetics and Developmental Biology, Innovation Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Dec 8;13:1026121. doi: 10.3389/fimmu.2022.1026121. eCollection 2022.
Allergic rhinitis (AR) and asthma are closely related, and AR is regarded as an important risk factor for the onset of asthma. However, the pathogenesis of the development of asthma from AR is still undefined.
The aim of this study was to investigate the mechanisms underlying the development of asthma from AR by comparing the transcriptome features of patients with AR with and without asthma.
Patients with AR with or without asthma caused by weed pollen who presented to the Allergy Clinic of Peking Union Medical College Hospital were recruited for this study. Peripheral blood samples of all the patients were collected during the weed pollen season (September) when the patients had allergic symptoms and outside the pollen season (November) when the patients had no symptoms. Transcriptomic analysis was conducted, and the differentially expressed genes (DEGs) and enriched immune pathways between the patients with AR with asthma (AR-asthma group) and those without asthma (AR group) were identified. In addition, the expression levels of some pivotal differentially expressed RNAs were quantified using quantitative polymerase chain reaction (PCR).
During the weed pollen season, the immune-related Gene Ontology (GO) terms with value < 0.05, enriched by the upregulated genes in the AR-asthma group compared to the AR group included antifungal humoral response, neutrophil-mediated killing of bacterium, antibacterial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptides, and regulation of the T cell receptor signaling pathway. The immune-related GO terms with values <0.05 enriched by downregulated genes were positive regulation of natural killer cell-mediated cytotoxicity, microglial cell activation, natural killer cell activation, and leukocyte-mediated cytotoxicity. The GO term of antimicrobial humoral immune response mediated by antimicrobial peptides was upregulated both during and outside the pollen season, and the upregulated expression of three DEGs (LTF, PF4, and ELANE) included in this term was verified through quantitative PCR.
The activation of the antimicrobial immune response mediated by neutrophils and the depression of cytotoxicity mediated by natural killer cells may play roles in the progression from AR to asthma.
变应性鼻炎（AR）和哮喘密切相关，AR 被认为是哮喘发病的重要危险因素。然而，AR 发展为哮喘的发病机制仍不明确。
本研究旨在通过比较花粉症患者伴哮喘和不伴哮喘的 AR 的转录组特征，探讨 AR 发展为哮喘的机制。
招募花粉症患者（杂草花粉），依据患者是否合并哮喘分为 AR 伴哮喘组（AR-asthma 组）和 AR 不伴哮喘组（AR 组）。两组患者均在花粉季节（9 月，有过敏症状时）和非花粉季节（11 月，无症状时）采集外周血。进行转录组分析，筛选出两组间差异表达基因（DEGs），并对富集的免疫途径进行分析。采用实时荧光定量聚合酶链反应（PCR）检测部分关键差异表达 RNA 的表达水平。
在花粉季节，与 AR 组相比，AR-asthma 组中上调基因富集到的与免疫相关的 Gene Ontology（GO）术语有抗真菌体液反应、中性粒细胞介导的杀菌、抗菌体液反应、抗菌肽介导的抗菌体液免疫反应和 T 细胞受体信号通路的调节，下调基因富集到的与免疫相关的 GO 术语有自然杀伤细胞介导的细胞毒性的正调控、小胶质细胞激活、自然杀伤细胞激活和白细胞介导的细胞毒性。抗菌肽介导的抗菌体液免疫反应在花粉季节和非花粉季节均上调，且该术语包含的 3 个 DEGs（LTF、PF4 和 ELANE）的表达水平通过定量 PCR 得到验证。
中性粒细胞介导的抗菌免疫反应的激活和自然杀伤细胞介导的细胞毒性的抑制可能在 AR 向哮喘的进展中起作用。
