儿童结核分枝杆菌不同感染状态下SEMA4A表达特征及其临床应用价值

doi:10.19982/j.issn.1000-6621.20260072

中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (7): 978-984.doi: 10.19982/j.issn.1000-6621.20260072

儿童结核分枝杆菌不同感染状态下SEMA4A表达特征及其临床应用价值

王文玉¹, 张同强²()

¹ 天津大学儿童医院/天津市儿童医院重症医学科, 天津市儿童出生缺陷防治重点实验室, 天津 300074
² 天津大学儿童医院/天津市儿童医院呼吸科, 天津市儿童出生缺陷防治重点实验室, 天津 300134

收稿日期:2026-02-02 出版日期:2026-07-10 发布日期:2026-07-02
通信作者: 张同强,Email:zhangqiang6612@126.com
基金资助:
天津市卫生健康科技项目(TJWJ2025RC013);天津市第二批卫生健康行业高层次人才选拔培养工程(TJSQNYXXR-D2-115);天津市医学重点学科建设资助(TJYXZDXK-3-016B)

Expression and diagnostic value of SEMA4A in children with different Mycobacterium tuberculosis infection statuses

Wang Wenyu¹, Zhang Tongqiang²()

¹ Department of Critical Care Medicine, Children’s Hospital, Tianjin University/Tianjin Children’s Hospital, Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300074, China
² Department of Pulmonology, Children’s Hospital, Tianjin University/Tianjin Children’s Hospital, Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China

Received:2026-02-02 Online:2026-07-10 Published:2026-07-02
Contact: Zhang Tongqiang, Email: zhangqiang6612@126.com
Supported by:
Tianjin Health Research Project(TJWJ2025RC013);The Second Selection and Training Program for High-Level Talents in Tianjin Health Sector(TJSQNYXXR-D2-115);Tianjin Key Medical Discipline Construction Project(TJYXZDXK-3-016B)

摘要/Abstract

摘要：

目的: 研究结核分枝杆菌不同感染状态下SEMA4A表达特征,明确SEMA4A在儿童活动性结核感染诊断中的应用价值。方法: 采用前瞻性研究方法,收集2020年4月至2025年10月在天津市儿童医院完成纤维支气管镜检查的645例患儿血清及支气管肺泡灌洗液(BALF)标本,建立样本库;参照入组标准最终纳入265例患儿,依据结核分枝杆菌感染状态将患儿分为活动性肺结核组(APTB组)、结核分枝杆菌潜伏感染组(LTBI组)、非结核呼吸道炎症疾病组(IDC组)及非感染非结核疾病对照组(NINTC组),采用频数匹配法确定各组相等样本量,最终每组各50例,共纳入200例。通过ELISA检测血清及BALF中SEMA4A浓度、qPCR检测BALF中SEMA4A mRNA水平、Western Blot检测BALF中SEMA4A表达水平,并绘制ROC曲线评价其检测效能。结果: ELISA检测4组血清SEMA4A表达浓度,结果显示APTB组SEMA4A水平[5.505(1.713,7.101)pg/ml]分别高于LTBI组[3.909(1.164,5.146)pg/ml]、IDC组[3.061(0.670,4.249)pg/ml]和NINTC组[2.350(1.103,3.153)pg/ml],差异均有统计学意义(Z=2.038,P=0.042;Z=2.684,P=0.007;Z=3.984,P<0.001);4组间差异也有统计学意义(H=9.327,P=0.025)。qPCR检测4组BALF中SEMA4A mRNA相对表达量,结果显示APTB组(6.112±0.440)分别高于LTBI组(4.124±0.272)、IDC组(2.086±0.517)、NINTC组(1.000±0.630),LTBI组分别高于IDC组和NINTC组,差异均有统计学意义(t=2.798,P=0.008;t=4.228,P<0.001;t=5.068,P<0.001;t=2.475,P=0.012;t=3.225,P=0.002),4组间差异也有统计学意义(F=128.387,P<0.001)。Western Blot检测4组BALF中SEMA4A相对表达量,结果显示APTB组(2.527±0.138)分别高于LTBI组(1.917±0.384)、IDC组(1.619±0.275)和NINTC组(1.000±0.370),LTBI组分别高于IDC组和NINTC组,差异均有统计学意义(t=2.566,P=0.014;t=3.936,P<0.001;t=4.637,P<0.001;t=2.194,P=0.029;t=2.984,P=0.005),4组间差异也有统计学意义(F=94.979,P<0.001)。ROC曲线分析显示,ELISA、qPCR和Western Blot检测SEMA4A的表达量对活动性结核病的AUC(95%CI)值分别为0.776(0.684~0.869)、 0.848(0.767~0.929)、0.821(0.736~0.906)。结论: 检测SEMA4A表达量可为儿童活动性结核病的诊断提供辅助依据,且采用qPCR检测BALF的效能最高。

关键词: 分枝杆菌感染, 带病原状态, 膜糖蛋白类, 儿童, SEMA4A

Abstract:

Objective: To explore the expression of SEMA4A in different Mycobacterium tuberculosis infection states and evaluate its diagnostic value for active tuberculosis in children. Methods: The study prospectively collected 645 children who underwent flexible bronchoscopy in Tianjin Children’s Hospital from April 2020 to October 2025, and specimens were stored to establish a specimen bank. Two hundred and sixty-five children who met the inclusion and exclusion criteria were classified into four groups: active pulmonary tuberculosis (APTB) group, latent tuberculosis infection (LTBI) group, non-tuberculous respiratory inflammatory disease control (IDC) group, and non-infectious and non-tuberculosis control (NINTC) group. Frequency matching was used for balanced grouping, and a total of 200 cases were finally included, 50 cases per group. The concentrations of SEMA4A from serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA. Level of SEMA4A mRNA from BALF was detected by qPCR, and SEMA4A protein expression by Western Blot. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic values. Results: The serum SEMA4A concentrations of the four groups measured by ELISA were: APTB group (5.505 (1.713, 7.101) pg/ml) was significantly higher than 3.909 (1.164, 5.146) pg/ml in the LTBI group, 3.061 (0.670, 4.249) pg/ml in the IDC group and 2.350 (1.103, 3.153) pg/ml in the NINTC group (Z=2.038, P=0.042; Z=2.684, P=0.007; Z=3.984, P<0.001). Overall inter-group difference among the four groups was statistically significant (H=9.327, P=0.025). qPCR detected average relative expression of SEMA4A mRNA in BALF of the APTB group was 6.112±0.440, higher than 4.124±0.272 in the LTBI group, 2.086±0.517 in the IDC group and 1.000±0.630 in the NINTC group. The LTBI group also had higher expression level compared with the IDC group and NINTC group, with all differences statistically significant (t=2.798, P=0.008; t=4.228, P<0.001; t=5.068, P<0.001; t=2.475, P=0.012; t=3.225, P=0.002). There was a significant difference among the four groups (F=128.387, P<0.001). Western Blot tested average relative expression of SEMA4A in BALF was 2.527±0.138 in the APTB group, which was higher than 1.917±0.384 in the LTBI group, 1.619±0.275 in the IDC group and 1.000±0.370 in the NINTC group. The LTBI group showed higher expression than the IDC group and NINTC group, and the differences were statistically significant (t=2.566, P=0.014; t=3.936, P<0.001; t=4.637, P<0.001; t=2.194, P=0.029; t=2.984, P=0.005). Significant inter-group difference was observed among the four groups (F=94.979, P<0.001).ROC curve analysis revealed that the AUC (95%CI) values of SEMA4A detected by ELISA, qPCR and Western Blot for active tuberculosis diagnosis were 0.776 (0.684-0.869), 0.848 (0.767-0.929) and 0.821 (0.736-0.906), respectively. Conclusion: Detection of SEMA4A expression can serve as an auxiliary indicator for the diagnosis of active tuberculosis in children, and qPCR assay of BALF exhibits the optimal diagnostic efficiency.

Key words: Mycobacterium infections, Carrier state, Membrane glycoproteins, Children, Semaphorin 4A

中图分类号:

王文玉, 张同强. 儿童结核分枝杆菌不同感染状态下SEMA4A表达特征及其临床应用价值[J]. 中国防痨杂志, 2026, 48(7): 978-984. doi: 10.19982/j.issn.1000-6621.20260072

Wang Wenyu, Zhang Tongqiang. Expression and diagnostic value of SEMA4A in children with different Mycobacterium tuberculosis infection statuses[J]. Chinese Journal of Antituberculosis, 2026, 48(7): 978-984. doi: 10.19982/j.issn.1000-6621.20260072

图/表 2

参考文献 28

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基本特征	APTB组 (50例)	LTBI组 (50例)	IDC组 (50例)	NINTC组 (50例)	统计检验值	P值
年龄(岁, $\bar{x}±s$)	5.3±2.5	6.2±3.5	5.5±2.8	5.3±3.2	F=1.045	0.386
性别[例(构成比,%)]					0.384	0.994
男性	24(48.0)	27(54.0)	26(52.0)	26(52.0)
女性	26(52.0)	23(46.0)	24(48.0)	24(48.0)
PPD试验[例(阳性率,%)]	43(86.0)	45(90.0)	0(0.0)	0(0.0)	-	<0.001
T-SPOT.TB[例(阳性率,%)]	38(76.0)	40(80.0)	0(0.0)	0(0.0)	-	<0.001
结核病接触史[例(发生率,%)]	18(36.0)	18(36.0)	0(0.0)	0(0.0)	-	<0.001
卡介苗接种史[例(发生率,%)]	48(96.0)	48(96.0)	50(100.0)	50(100.0)	-	0.330
卡痕[例(发生率,%)]	46(92.0)	49(98.0)	50(100.0)	50(100.0)	-	0.055
基础疾病[例(发生率,%)]	3(6.0)	0(0.0)	0(0.0)	0(0.0)	/	/

儿童结核分枝杆菌不同感染状态下SEMA4A表达特征及其临床应用价值

Expression and diagnostic value of SEMA4A in children with different Mycobacterium tuberculosis infection statuses

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