Supplementary Material for: Characteristics of asthmatic patients with IL18R1 differential expression in induced sputum

Background: IL18R1 is involved in the pathogenesis of asthma and atopic phenotypes. However, IL18R1 expression level in induced sputum supernatant of asthma remains unclear.
Methods: IL18R1, IL-4, IL-5, IL-13, IFN-r, and MUC5AC protein expression in induced sputum supernatant was detected by ELISA in patients with asthma, and the correlation of IL18R1 expression with clinical parameters (FeNO, peripheral blood eosinophil count, serum IgE, and lung function), Th1 cytokine (IFN-r), Th2 cytokine (IL-4, IL-5, and IL-13) and mucus (MUC5AC) were analyzed. Asthma subjects were categorized as IL18R1low and IL18R1high (below or above the upper quartile of the control group, respectively). Clinical features were compared between the IL18R1low and IL18R1high asthma subgroups. Subjects with asthma underwent a 4-week treatment with inhaled budesonide.
Results: We found that IL18R1 level in induced sputum increased and was correlated with FeNO, peripheral blood eosinophil count, serum IgE, FEV1 (%predicted), FEV1/FVC%, and Th2 cytokine (IL-4, IL-5, and IL-13) expression in patients with asthma. IL18R1 expression was not correlated with Th1 cytokine IFN-r and MUC5AC in induced sputum. IL18R1high asthma had higher FeNO levels, higher peripheral blood eosinophil counts, lower FEV1/FVC%, and higher Th2 cytokine (IL-4, IL-5, and IL-13) expression than IL18R1low subgroup or controls. IL18R1high asthma had a significant decrease in FeNO and more improvement in FEV1 during inhaled corticosteroid (ICS) treatment compared with patients having the IL18R1low subgroup.
Conclusions: IL18R1 level in induced sputum was increased. IL18R1low and IL18R1high asthma subgroups had different clinical features and responses to ICS treatment. IL18R1 level in induced sputum may be a novel marker of Th2-high asthma and has potential application in predicting treatment response.

背景：白细胞介素18受体1（IL18R1）参与哮喘与特应性表型的发病机制，但目前哮喘患者诱导痰上清液中IL18R1的表达水平仍不明确。
方法：采用酶联免疫吸附试验（ELISA）检测哮喘患者诱导痰上清液中IL18R1、IL-4、IL-5、IL-13、干扰素γ（IFN-γ）及黏蛋白5AC（MUC5AC）的蛋白表达水平，并分析IL18R1表达与临床参数（呼出气一氧化氮（FeNO）、外周血嗜酸性粒细胞计数、血清IgE、肺功能）、Th1细胞因子（IFN-γ）、Th2细胞因子（IL-4、IL-5、IL-13）及黏蛋白（MUC5AC）的相关性。将哮喘受试者按IL18R1表达水平分为低表达组（IL18R1low）与高表达组（IL18R1high），分别对应低于或高于对照组上四分位数水平。比较两组哮喘亚组的临床特征。所有哮喘受试者接受为期4周的吸入布地奈德治疗。
结果：本研究发现，哮喘患者诱导痰中的IL18R1水平升高，且其表达与FeNO、外周血嗜酸性粒细胞计数、血清IgE、第1秒用力呼气容积占预计值百分比（FEV1%pred）、FEV1/FVC比值及Th2细胞因子（IL-4、IL-5、IL-13）的表达水平显著相关。诱导痰中IL18R1的表达与Th1细胞因子IFN-γ及MUC5AC无明显相关性。与IL18R1低表达组及对照组相比，IL18R1高表达型哮喘患者的FeNO水平更高、外周血嗜酸性粒细胞计数更多、FEV1/FVC比值更低，且Th2细胞因子（IL-4、IL-5、IL-13）表达水平更高。与IL18R1低表达组患者相比，IL18R1高表达型哮喘患者在接受吸入性糖皮质激素（ICS）治疗期间，FeNO水平下降更显著，FEV1改善更明显。
结论：哮喘患者诱导痰中的IL18R1水平升高。IL18R1低表达与高表达哮喘亚组具有不同的临床特征及对ICS治疗的应答反应。诱导痰中IL18R1水平或可作为Th2高表型哮喘的新型标志物，在预测治疗应答方面具有潜在应用价值。