Laboratory of Allergic Diseases, La Jolla Institute for Immunology, La Jolla, Calif.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pa.
J Allergy Clin Immunol. 2023 Sep;152(3):633-640.e4. doi: 10.1016/j.jaci.2023.04.021. Epub 2023 Jun 8.
Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma.
We aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations.
Total IgE and HRF-reactive IgE/IgG as well as HRF in sera from patients with mild/moderate asthma or severe asthma (SA) and healthy controls (HCs) were quantified by ELISA. HRF secretion in culture media from RV-infected adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by Western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified.
HRF-reactive IgE and total IgE levels were higher in patients with SA than in HCs, whereas HRF-reactive IgG (and IgG) level was lower in asthmatic patients versus HCs. In comparison with HRF-reactive IgE asthmatic patients, HRF-reactive IgE asthmatic patients had a tendency to release more tryptase and prostaglandin D on anti-IgE stimulation of bronchoalveolar lavage cells. RV infection induced HRF secretion from adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections.
HRF-reactive IgE is higher in patients with SA. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.
组氨酸释放因子（HRF）与过敏疾病有关。我们之前在哮喘的小鼠模型中显示了其致病作用。
我们旨在呈现来自 3 个人类样本（哮喘患者的血清样本、鼻病毒（RV）感染个体的鼻腔冲洗液和 RV 引起的哮喘加重患者的血清样本）和 1 个小鼠样本的数据分析，以研究 HRF 功能在哮喘和病毒引起的哮喘加重中的相关性。
通过 ELISA 定量测定轻度/中度哮喘或严重哮喘（SA）患者和健康对照者（HCs）的血清中总 IgE 和 HRF 反应性 IgE/IgG 以及 HRF。通过 Western 印迹分析 RV 感染的腺病毒-12 SV40 杂交病毒转化的人支气管上皮细胞培养物中的 HRF 分泌和 RV 感染的实验对象的鼻腔冲洗液中的 HRF 分泌。还定量测定了哮喘加重患者的纵向血清样本中的 HRF 反应性 IgE/IgG 水平。
与 HCs 相比，SA 患者的 HRF 反应性 IgE 和总 IgE 水平更高，而哮喘患者的 HRF 反应性 IgG（和 IgG）水平低于 HCs。与 HRF 反应性 IgE 哮喘患者相比，HRF 反应性 IgE 哮喘患者在抗 IgE 刺激支气管肺泡灌洗液细胞时更倾向于释放更多的类胰蛋白酶和前列腺素 D。RV 感染诱导腺病毒-12 SV40 杂交病毒转化的支气管上皮细胞中 HRF 的分泌，并且 RV 对人体的鼻内感染增加了鼻冲洗液中 HRF 的分泌。与 RV 感染消退后相比，RV 感染相关哮喘加重时哮喘患者的 HRF 反应性 IgE 水平更高。在没有病毒感染的哮喘加重中，并未出现这种现象。
SA 患者的 HRF 反应性 IgE 更高。RV 感染诱导呼吸道上皮细胞中 HRF 的分泌，无论是在体外还是在体内。这些结果表明 HRF 在哮喘严重程度和 RV 引起的哮喘加重中的作用。
