Kong Y, Zhang T Z, An X Y, Wu J, Ye X L
Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Zhonghua Er Ke Za Zhi. 2025 Jul 2;63(7):759-764. doi: 10.3760/cma.j.cn112140-20241217-00922.
To evaluate the characteristics of neutrophil extracellular traps (NET) in children with inflammatory bowel disease (IBD) and its role in diagnosis and disease activity monitoring. A total of 66 IBD children admitted to Beijing Children's Hospital from December 2017 to August 2024 were enrolled in this cross-sectional study, another 20 age-matched children who underwent gastrointestinal endoscopy during the same period in the same hospital and showed no abnormalities were selected as the controls. Clinical data of IBD and control group were collected. Children with IBD were divided into active group and remission group according to clinical score and endoscopic score. The peripheral blood of IBD and control group were collected, and the levels of NET markers, including neutrophil elastase (NE) and myeloperoxidase (MPO)-DNA were detected by enzyme-linked immunosorbent assay. The levels of NET markers in control group and different IBD groups were compared. Independent sample -test or Mann-Whitney test was used for group comparisons. Kruskal-Wallis test was used for multiple group comparisons. Spearman correlation analysis was used to analyze the correlation between NET markers and IBD activity. The efficacy of laboratory indicators in diagnosing IBD and control group was evaluated using receiver operating characteristic (ROC) curve. There were 66 children with IBD, including 36 in Crohn's disease group with the age of (11.0±3.7) years, and 30 in ulcerative colitis (UC) group with the age of (8.3±5.0) years. The control group consisted of 20 children with the age of (10.1±3.5) years. Compared with control group, the levels of NE (958 (771, 1 328) 303 (196, 501) μg/L) and MPO-DNA (0.11 (0.09, 0.18) 0.09 (0.06, 0.12)) in peripheral blood of IBD group were significantly higher (both <0.05). However, there was no significant difference in the levels of NE (1 008 (863, 1 301) 807 (567, 1 535) μg/L) and MPO-DNA (0.11 (0.09, 0.21) 0.12 (0.09, 0.14)) between Crohn's disease and UC groups (both >0.05). The NE levels in the endoscopic active group and remission group of Crohn's disease were higher than those in the control group (both <0.05). The MPO-DNA level in the endoscopic active group of Crohn's disease was higher than that in the control group (<0.05), while the MPO-DNA level in the endoscopic remission group of Crohn's disease was lower than that in the control group (>0.05). The NE levels in the endoscopic activity group and remission group of UC were higher than those in control group (both <0.05). NET markers were not correlated with the clinical activity and endoscopic activity of IBD (all >0.05). ROC curve analysis showed that the area under the curve of NE combined with MPO-DNA for distinguishing IBD from controls was 0.95, with a sensitivity was 90.0% and a specificity was 89.4%. The combination of NE and MPO-DNA demonstrated high sensitivity and specificity for distinguishing pediatric IBD patients from healthy children, suggesting its potential as a diagnostic biomarker panel of IBD.
评估炎症性肠病(IBD)患儿中性粒细胞胞外陷阱(NET)的特征及其在诊断和疾病活动监测中的作用。本横断面研究纳入了2017年12月至2024年8月在北京儿童医院住院的66例IBD患儿,另选取同期在同一家医院接受胃肠内镜检查且无异常的20例年龄匹配儿童作为对照。收集IBD组和对照组的临床资料。根据临床评分和内镜评分将IBD患儿分为活动组和缓解组。采集IBD组和对照组的外周血,采用酶联免疫吸附测定法检测NET标志物水平,包括中性粒细胞弹性蛋白酶(NE)和髓过氧化物酶(MPO)-DNA。比较对照组和不同IBD组的NET标志物水平。组间比较采用独立样本t检验或Mann-Whitney检验。多组比较采用Kruskal-Wallis检验。采用Spearman相关性分析分析NET标志物与IBD活动度之间的相关性。采用受试者工作特征(ROC)曲线评估实验室指标对IBD组和对照组的诊断效能。共有66例IBD患儿,其中克罗恩病组36例,年龄为(11.0±3.7)岁,溃疡性结肠炎(UC)组30例,年龄为(8.3±5.0)岁。对照组由20例年龄为(10.1±3.5)岁的儿童组成。与对照组相比,IBD组外周血NE水平(958(771,1328)对303(196,501)μg/L)和MPO-DNA水平(0.11(0.09,0.18)对0.09(0.06,0.12))显著更高(均P<0.05)。然而,克罗恩病组和UC组之间的NE水平(1008(863,1301)对807(567,1535)μg/L)和MPO-DNA水平(0.11(0.09,0.21)对0.12(0.09,0.14))无显著差异(均P>0.05)。克罗恩病内镜活动组和缓解组的NE水平均高于对照组(均P<0.05)。克罗恩病内镜活动组的MPO-DNA水平高于对照组(P<0.05),而克罗恩病内镜缓解组的MPO-DNA水平低于对照组(P>0.05)。UC内镜活动组和缓解组的NE水平均高于对照组(均P<0.05)。NET标志物与IBD的临床活动度和内镜活动度均无相关性(均P>0.05)。ROC曲线分析显示,NE联合MPO-DNA区分IBD与对照组的曲线下面积为0.95,灵敏度为90.0%,特异度为89.4%。NE和MPO-DNA联合检测对区分小儿IBD患者与健康儿童具有较高的灵敏度和特异度,提示其作为IBD诊断生物标志物组合的潜力。