目的: 分析儿童支气管哮喘(BA)患者中血清趋化因子配体19(CCL19)和趋化因子配体21(CCL21)的表达,探讨其在儿童BA中可能介导的病理过程及其在哮喘中是否具有临床指导意义。方法: 收集2021年7月至2022年12月于包头市第四医院就诊的BA儿童共72例作为哮喘组,其中急性发作期(AA)32例,临床缓解期(CR)40例;同期选取正常体检儿童33例作为正常对照组(HC)。所有入组儿童均采用ELISA法检测CCL19、CCL21水平,行统计学比较,并评价CCL19、CCL21在儿童支气管哮喘中的诊断效能。结果: (1)各组间血清CCL19、CCL21表达水平比较,差异有统计学意义(P＜0.05),其中哮喘组血清CCL19、CCL21表达水平均高于HC组,且AA组又高于CR组;(2)BA儿童CCL19、CCL21水平呈正相关(r=0.819,P＜0.05);(3)ROC曲线结果显示,CCL19诊断曲线下面积(AUC)为0.797,最佳截断值为131.58 pg/mL,其敏感度为79.2 %,特异度为69.7 %;CCL21的AUC为0.771,最佳截断值为307.33 pg/mL,其敏感度及特异度分别为69.4 %、84.8 %。结论: (1)血清CCL19和CCL21表达水平在支气管哮喘患儿中明显升高,且两者间呈正向相关,提示CCL19与CCL21可能参与哮喘发病机制的过程;(2)ROC曲线提示血清CCL19与CCL21具有良好的诊断效能,提示二者可能成为诊断哮喘及评估临床治疗效果的一个新的实验室依据。
Objective: To analyze the expression of serum C-C chemokine ligand 19 (CCL19) and C-C chemokine ligand 21 (CCL21) in children with bronchial asthma (BA), and to explore its possible mediated pathological process in children with BA, and whether it has clinical guiding significance in asthma. Methods: A total of 72 BA children who were treated in Baotou Fourth Hospital from July 2021 to December 2022 were collected as the asthma group, including 32 cases of acute exacerbation (AA) and 40 cases of clinical remission (CR). At the same time, 33 children with normal physical examination were selected as normal control group (HC). The levels of CCL19 and CCL21 were detected by ELISA in all enrolled children, and the diagnostic efficacy of CCL19 and CCL21 in children with bronchial asthma was evaluated. Results: (1)There were significant differences in the expression levels of serum CCL19 and CCL21 among the three groups (P＜0.05), while the expression levels of serum CCL19 and CCL21 in the asthma group were higher than those in the HC group, and those in the AA group were higher than those in the CR group. (2)The levels of CCL19 and CCL21 in BA children were positively correlated (r=0.819, P＜0.05). (3)The results of ROC curve showed that the area under the curve (AUC) of CCL19 was 0.797, the optimal cut-off value was 131.58 pg/mL, the sensitivity was 79.2 %, and the specificity was 69.7 %. The AUC of CCL21 was 0.771, the optimal cut-off value was 307.33 pg/mL, and the sensitivity and specificity were 69.4 % and 84.8 %, respectively. Conclusion: (1) The expression levels of serum CCL19 and CCL21 are significantly increased in children with bronchial asthma, and there is a positive correlation between them, suggesting that CCL19 and CCL21 may be involved in the pathogenesis of asthma. (2) The ROC curve shows that serum CCL19 and CCL21 had good diagnostic efficacy, suggesting that they may become a new laboratory basis for the diagnosis of asthma and the evaluation of clinical treatment.
[1] Martin J, PijnenburgMW, Roberts G, et al. Does lung function change in the months after an asthma exacerbation in children[J]. Pediatr Allergy Immunol, 2021,32(6):1208-1216.
[2] 刘璟,田冰. 树突状细胞在儿童变应性哮喘中的表达及意义[J]. 中国现代医学杂志,2018,28(2):65-68.
[3] Ferraro VA, Zanconato S, Baraldi E, et al. Nitric oxide and biological mediators in pediatric chronic rhinosinusitis and asthma[J]. J Clin Med, 2019,8(11):1783.
[4] Galiniak S, Biesiadecki M, Aebisher D, et al. Nasal nitric oxide in upper airways in children with asthma and allergic rhinitis[J]. Adv Med Sci, 2020,65(1):127-133.
[5] Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases[J]. Lancet, 2018,391(10118):350-400.
[6] 刘梅,张善林,邵宪辉. 血清趋化因子CCL19、CCL21与儿童支气管哮喘病情的相关性[J]. 中华肺部疾病杂志(电子版),2020,13(3):379-381.
[7] Zhang S, Wang HZ, Xu ZY, et al. Lymphatic metastasis of NSCLC involves chemotaxis effects of lymphatic endothelial cells through the CCR7-CCL21 axis modulated by TNF-α[J]. Genes, 2020,11(11):1309.
[8] 中华儿科杂志编辑委员会,中华医学会儿科学分会呼吸学组,中国医师协会儿科医师分会儿童呼吸专业委员会. 儿童支气管哮喘规范化诊治建议(2020年版)[J]. 中华儿科杂志,2020,58(9):708-717.
[9] 张倩倩,柴向斌. 趋化因子配体CCL21与慢性炎症性疾病的关系[J]. 中华临床免疫和变态反应杂志,2021,15(2):207-212.
[10] Boulet LP. Effects of steroid therapy on inflammatory cell subtypes in asthma[J]. Thorax, 2010,65(5):374-376.
[11] Wang Q, Zhang W J, Liu LL, et al. Effects of physical therapy on lung function in children with asthma:Study protocol for a systematic review and meta-analysis[J]. Medicine, 2019,98(15):e15226.
[12] Zhang Y, Xu Y, Liu SW, et al. Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma[J]. Cell Res, 2016,26(11):1226-1241.
[13] Zhang JF, Li Y, Zhang AZ, et al. Expression and pathological significance of CC chemokine receptor 7 and its ligands in the airway of asthmatic rats exposed to cigarette smoke[J]. J Thorac Dis, 2018,10(9):5459-5467.
[14] Leon B. T Cells in Allergic Asthma: Key players beyond the Th2 pathway[J]. Curr Allergy Asthma Rep, 2017,17(7):43.
[15] Zhang W, Tu GJ, Lv C, et al. Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration[J]. BiochemBiophys Res Commun, 2014,451(2):222-228.
[16] Lou YY, Zheng Y, Xu YH, et al. Association of serum chemokine ligand 21 levels with asthma control in adults[J]. Clinics, 2021,76:e1713.
[17] Liu JQ, Wei Y, Luo QL, et al. Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-κB and suppressing CCR7/CCL19/CCL21[J]. Int J Mol Med, 2016,38(5):1541-1548.
[18] Yamashita N, Tashimo H, Matsuo Y, et al. Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model[J]. J Allergy Clin Immunol, 2006,117(5):1040-1046.
