The role of inducible costimulatory molecular ligand (ICOSL) in children with neutrophilic asthma
The role of inducible costimulatory molecular ligand (ICOSL) in children with neutrophilic asthma
复制标题
诱导共刺激分子配体（ICOSL）在中性粒细胞性哮喘儿童中的作用
DOI：
10.21037/tp-20-172
复制
发表时间：
2020-08-01
影响因子：
2
通讯作者：
Chen, Zhengrong
中科院分区：
文献类型：
--
作者：
Dong, Heting;Wang, Ting;Chen, Zhengrong
背景研究表明，某些重症和难治性哮喘是由中性粒细胞而不是嗜酸性粒细胞浸润引起的。可诱导共刺激分子配体(ICOSL)的表达与肿瘤和自身免疫性疾病密切相关，但有关ICOSL在儿童中性粒细胞哮喘中的意义的数据有限。本研究旨在探讨中性粒细胞哮喘患儿外周血和支气管肺泡灌洗液(BALF)中ICOSL异常表达的临床意义。方法选择苏州大学儿童医院符合哮喘诊断标准的患儿，排除病原学阳性的患儿。同期因吸入异物入院的患儿为对照组。中性粒细胞在BALF样本中超过50%的儿童被分为中性粒细胞哮喘组(NA组)，其余受试者组成哮喘组(A组)。采用双抗体夹心法检测中性粒细胞哮喘患儿血浆和肺泡灌洗液中ICOSL、IL-4、IL-17、干扰素-γ、中性粒细胞弹性蛋白酶(NE)、基质金属蛋白酶-9(MMP9)的表达水平，分析中性粒细胞哮喘与非中性粒细胞哮喘患儿细胞因子水平及临床特征的差异。此外，还探讨了ICOSL在中性粒细胞哮喘中的可能机制。结果共纳入32名儿童，NA组12名，A组20名。NA组平均住院时间长于A组(P<；0.05)。NA组血浆和肺泡灌洗液中ICOSL、IL-17、NE和MMP9水平均高于A组，而干扰素-γ水平则相反。NA组ICOSL与血浆(r=0.753，P=0.012)和肺泡灌洗液(r=0.774，P=0.009)中IL-17水平呈显著正相关。结论中性粒细胞哮喘患儿病情较重，临床治疗难度较大，住院时间较长。ICOSL可能通过调节Th17分泌IL-17，增加中性粒细胞中NE和MMP9水平，参与中性粒细胞免疫炎症的发生。
Background It has been shown that certain severe and refractory asthma cases are caused by neutrophil and not eosinophil infiltration. Inducible costimulatory molecular ligand (ICOSL) expression is closely associated with tumor and autoimmune diseases, yet a limited amount of data has been published regarding the significance of ICOSL in children with neutrophilic asthma. The present study aimed to explore the clinical significance of abnormal expression of ICOSL in peripheral blood and bronchoalveolar lavage fluid (BALF) samples of children with neutrophilic asthma. Methods Selected children from the Children’s Hospital of Soochow University who met the diagnostic criteria of asthma and excluded patients with a pathogen-positive etiology. Children who were admitted to the hospital for foreign body inhalation in the same period acted as the control group. Children with more than 50% of neutrophils in BALF samples were assigned to the neutrophilic asthma group (NA group), and the remaining subjects composed the asthma group (A group). The expression levels of ICOSL, IL-4, IL-17, IFN-γ, neutrophil elastase (NE), and matrix metalloproteinase-9 (MMP-9) were detected in plasma and BALF samples by enzyme-linked immunosorbent assays, in order to analyze the differences in the levels of cytokines and clinical characteristics between children with neutrophilic asthma and non-neutrophilic asthma. Moreover, the potential mechanism of ICOSL in neutrophilic asthma was explored. Results 32 children were enrolled: 12 children in the NA group and 20 children in the A group. The mean hospitalization time of the NA group was longer than that of the A group (P<0.05). The concentration levels of ICOSL, IL-17, NE, and MMP-9 in plasma and BALF samples in the NA group were higher than those in the A group, while the levels of IFN-γ exhibited opposite. A significant correlation was found between ICOSL and IL-17 levels in plasma (r=0.753, P=0.012) and BALF (r=0.774, P=0.009) samples in the NA group. Conclusions Children with neutrophilic asthma were more severely affected, experiencing a considerably more difficult clinical treatment and longer hospitalization time. ICOSL may regulate the secretion of IL-17 by Th17 and increase the levels of NE and MMP-9, which are involved in the development of immune inflammation in neutrophils.