嗜酸粒细胞型哮喘患儿外周血单个核细胞肿瘤坏死因子α诱导蛋白8样分子2 mRNA和M2巨噬细胞检测及意义

Detection and significance of TIPE2 mRNA and M2 macrophagesin peripheral blood mononuclear cells of children with eosinophilic asthma

目的:检测嗜酸粒细胞型哮喘(EA)患儿外周血单个核细胞(PBMC)肿瘤坏死因子α诱导蛋白8样分子2(TIPE2)mRNA和M2巨噬细胞,并分析其意义。方法:回顾性收集EA患儿100例,根据糖皮质激素(ICS)治疗后2周内症状缓解情况,分为完全缓解组(78例)和部分缓解组(22例)。另选取体检健康儿童52例,设为对照组。比较三组临床资料[肺功能、血常规、呼出气一氧化氮(FeNO)]、TIPE2 mRNA、M2巨噬细胞占比、治疗前后免疫细胞[辅助性T细胞1(Th1)、辅助性T细胞2(Th2)]以及细胞因子[白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)、IL-4、IL-13、精氨酸酶1(Arg-1)]。分析EA患儿预后的影响因素,并进行相关性分析。结果:完全缓解组和部分缓解组用力肺活量(FVC)、呼吸流量峰值(PEF)、第1秒用力呼气容积(FEV1)、嗜酸性粒细胞(EOS)、淋巴细胞(LYM)、白细胞(WBC)、FeNO与对照组比较差异有统计学意义(均P<0.05),但两组间上述指标比较差异无统计学意义(均P>0.05)。治疗前,完全缓解组与部分缓解组TIPE2 mRNA、M2巨噬细胞占比、M2/M1、IL-4、IL-13、IL-2、Arg-1高于对照组,Th1、Th1/Th2、IFN-γ低于对照组,且完全缓解组TIPE2 mRNA、M2巨噬细胞、Th1、IL-4、IL-13、Arg-1与部分缓解组比较差异有统计学意义(均P<0.05)。治疗后,完全缓解组和部分缓解组TIPE2 mRNA、M2巨噬细胞占比、M2/M1、IL-4、IL-13、IL-2、Arg-1降低,Th1、Th1/Th2、IFN-γ升高,且完全缓解组与部分缓解组比较差异有统计学意义(均P<0.05)。Logistic回归分析结果显示,TIPE2 mRNA、M2巨噬细胞、IL-4、IL-13、Arg-1为EA患儿预后的影响因素(均P<0.05)。Pearson分析结果显示,M2巨噬细胞与IL-4、IL-13呈负相关,与TIPE2 mRNA、Arg-1呈正相关;TIPE2 mRNA与IL-4、IL-13的水平呈负相关(均P<0.05)。结论:EA患儿PBMC中TIPE2 mRNA与M2巨噬细胞呈高表达,均为影响预后的因素。

Objective:To detect tumor necrosis factorα-induced protein 8-like molecule 2(TIPE2)mRNA and M2 macrophages in peripheral blood mononuclear cells(PBMC)of children with eosinophilic asthma(EA),and to analyze their significance.Methods:A retrospective analysis was performed for the clinical data of 100 children with EA.According to whether the symptoms were relieved within 2 weeks of glucocorticoid(ICS)treatment,they were divided into complete remission group with 78 children and partial remission group with 22 children.Another 52 healthy subjects were selected as the control group.The clinical data(lung function,blood routine,and FeNO),TIPE2 mRNA,the proportion of M2 macrophages,immune cells(Th1 and Th2)and cytokines(IL-2,IFN-γ,IL-4,IL-13,Arg-1)before and after treatment were compared among the three groups.The prognostic factors of children with EA were analyzed,and the correlation was analyzed.Results:There were significant differences in FVC,PEF,FEV1,EOS,LYM,WBC and FeNO between the complete remission group,the partial remission group and the control group(all P<0.05),but there were no significant differences in the above indicators between the two groups(all P>0.05).Before treatment,TIPE2 mRNA,M2 macrophage ratio,M2/M1,IL-4,IL-13,IL-2,Arg-1,and Th1,Th1/Th2,IFN-γin complete and partial response groups were higher than those in control group,and lower than those in control group,and TIPE2 mRNA,M2 macrophages,Th1,IL-4,IL-13 and Arg-1 in complete remission group were significantly different from those in partial remission group(all P<0.05).After treatment,TIPE2 mRNA,M2 macrophage proportion,M2/M1,IL-4,IL-13,IL-2,Arg-1,and Th1,Th1/Th2,IFN-γwere decreased in the complete remission group and the partial remission group,and the difference between the complete remission group and the partial remission group was statistically significant(all P<0.05).Logistic regression analysis showed that TIPE2 mRNA,M2 macrophages,IL-4,IL-13 and Arg-1 were the prognostic factors of EA children(all P<0.05).Pearson analysis showed that M2 macrophages were negatively correlated with IL-4 and IL-13,and positively correlated with TIPE2 mRNA and Arg-1;TIPE2 mRNA was negatively correlated with IL-4 and IL-13 levels(all P<0.05).Conclusion:TIPE2 mRNA and M2 macrophages were highly expressed in PBMC of children with EA,both of which were prognostic factors.