切换至 "中华医学电子期刊资源库"

中华临床实验室管理电子杂志 ›› 2020, Vol. 08 ›› Issue (01) : 13 -17. doi: 10.3877/cma.j.issn.2095-5820.2020.01.003

所属专题: 文献

实验研究

外周血单核细胞及相关细胞因子检测在肺结核中的临床价值
沈甜1, 张海云1, 顾德林1, 朱易华2, 陶国华2, 陈俊林3, 喻禹4, 蔡慧慧1, 曹兴建2,()   
  1. 1. 226011 江苏南通市,南通市第六人民医院检验科
    2. 226001 江苏南通市,南通大学附属第二医院检验科
    3. 226011 江苏南通市,南通市第六人民医院结核科
    4. 226011 江苏南通市,南通市第六人民医院信息科
  • 收稿日期:2019-08-06 出版日期:2020-02-28
  • 通信作者: 曹兴建
  • 基金资助:
    2018年南通市卫生和计划生育委员会科研课题(No.WKZL2018068)

Clinical value of monocytes and related cytokines in peripheral blood in pulmonary tuberculosis

Tian Shen1, Haiyun Zhang1, Delin Gu1, Yihua Zhu2, Guohua Tao2, Junlin Chen3, Yu Yu4, Huihui Cai1, Xingjian Cao2,()   

  1. 1. Department of Laboratory, The Sixth People's Hospital of Nantong, Nantong Jiangsu 226011, China
    2. Department of Laboratory, The Second Affiliated Hospital of Nantong University, Nantong Jiangsu 226001, China
    3. Department of Tuberculosis, The Sixth People's Hospital of Nantong, Nantong Jiangsu 226011, China
    4. Department of Information, The Sixth People's Hospital of Nantong, Nantong Jiangsu 226011, China
  • Received:2019-08-06 Published:2020-02-28
  • Corresponding author: Xingjian Cao
  • About author:
    Corresponding author: Cao Xingjian, Email:
引用本文:

沈甜, 张海云, 顾德林, 朱易华, 陶国华, 陈俊林, 喻禹, 蔡慧慧, 曹兴建. 外周血单核细胞及相关细胞因子检测在肺结核中的临床价值[J]. 中华临床实验室管理电子杂志, 2020, 08(01): 13-17.

Tian Shen, Haiyun Zhang, Delin Gu, Yihua Zhu, Guohua Tao, Junlin Chen, Yu Yu, Huihui Cai, Xingjian Cao. Clinical value of monocytes and related cytokines in peripheral blood in pulmonary tuberculosis[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2020, 08(01): 13-17.

目的

回顾性分析初治活动性肺结核(APTB)患者与健康体检者外周血单核细胞及相关细胞因子的动态变化,探讨两者的相关性及临床应用价值。

方法

使用迈瑞BC-6900全自动血细胞分析仪检测72例APTB患者(病例组)和79例健康体检者(正常对照组)的外周血血常规,记录单核细胞计数(MO#)和单核细胞百分率(MO%);测定两组血清白介素-1β(IL-1β)、白介素-6(IL-6)以及肿瘤坏死因子-α (TNF-α)表达水平,然后进行组间指标比较分析,并对单核细胞参数和细胞因子浓度进行相关性分析,同时绘制受试者工作特征(ROC)曲线,评价各指标诊断APTB的敏感度和特异度。

结果

病例组外周血MO%、MO#明显高于正常对照组(t值分别为5.135、5.510,P值均<0.05),APTB患者血清IL-1β、IL-6以及TNF-α浓度与正常对照相比,均发生了明显升高,差异具有统计学意义(U=405.000、P<0.001,U=543.500、P<0.001,U=563.000、P<0.001)。APTB患者外周血MO#与血清IL-6表达水平呈弱负相关(r=-0.247、P<0.05)。项目间诊断性能比较分析显示,指标IL-1β、IL-6以及TNF-α的曲线下面积(AUC)分别为0.891、0.918和0.887均高于MO%和MO#(AUC分别为0.758、0.735)。当IL-1β临界值取9.017 ng/L时,其诊断APTB的敏感度为83.3%,特异度为81.2%;当IL-6临界值取3.835 ng/L时,诊断APTB的敏感度为86.1%,特异度为84.4%;当TNF-α临界值取138.545 ng/L时,其诊断APTB的敏感度为80.6%,特异度为81.2%,均优于MO%(65.3%、62.0%)和MO#(70.8%、64.6%)。此外,同时测量IL-1β,IL-6和TNF-α可获得的曲线下面积高达0.987,其诊断APTB的灵敏度和特异度分别为95.8%和92.8%。

结论

结核分枝杆菌感染机体引起APTB,外周血单核细胞迁移至肺泡从而衍变为巨噬细胞(M?),活化M?产生一系列细胞因子,在机体循环池单核细胞数目变化中可能产生了一定影响,可以作为区分APTB和正常人群的理想标志物。

Objective

To analyze the dynatic changes of monocytes and related cytokines in peripheral blood of patients with active pulmonary tuberculosis (APTB) and in peripheral blood of healthy people retrospectively, so as to explore the correlation between the diseases and the cells, the cytokines, and investigate their clinical application value.

Methods

Peripheral blood specimens from 72 patients with APTB and 79 healthy controls were measured by using Myrtle BC-6900 automatic hematology analyzer. Percentage of monocyte (MO%) and monocyte counts (MO#) were recored by the analyzer. Serum levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) were measured in the two groups. Then comparative analysis of the inter-group index was carried out, and the correlation between monocyte parameters and cytokine concentration was analyzed. Operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of each index in the diagnosis of APTB.

Results

The peripheral blood Mo% and Mo# in the case group were significantly higher than those in the normal control group (t=5.135, P<0.001 and t=5.510, P<0.001). The serum IL-1β、IL-6 and TNF-α concentrations in the patients with APTB were significantly higher than those in healthy controls and the different was statistically signtficant (U=405.000, P<0.001, U=543.500, P<0.001, and U=563.000, P<0.001). There was a weak negative correlation between Mo# and IL-6 (r=-0.247、P<0.05). A comparative analysis of diagnostic performance between projects showed that AUCs of IL-1β, IL-6 and TNF-α (AUC=0.891, 0.918 and 0.887 respectively) were higher than that of MO% and MO# (AUC=0.758 and 0.735, respectively).When the critical value of IL-1β was 9.0175 ng/l, the sensitivity and specificity of diagnosing APTB were 83.3% and 81.2% respectively; when the critical value of IL-6 was 3.835 ng/l, the sensitivity and specificity of the diagnosing APTB were 86.1% and 84.4% respectively; when the critical value of TNF-α was 138.545 ng/l, the sensitivity and specificity of diagnosing APTB were 80.6% and 81.2%, which were superior to MO% (65.3% vs. 62.0%) and MO# (70.8% vs. 64.6%). In addition, the area under the curve obtained by simultaneous measurement of IL-1β, IL-6 and TNF-α was as high as 0.987, and the sensitivity and specificity of diagnosing APTB were 95.8% and 92.8%, respectively.

Conclusion

During APTB, the peripheral blood mononuclear cells (MO) may migrate to the alveoli and then evolve into macrophages (M?) and the activated M? may produce a series of cytokines, which may have a certain impact on the number of monocytes in the circulating pool and can be used as an ideal marker to distinguish APTB from the normal individuals.

表1 病例组和正常对照组单核细胞及相关细胞因子浓度比较
图1 血清CK诊断APTB的ROC曲线
表2 各参数的ROC曲线AUC及最佳临界值
1
Shen T, Cao X, Shi J, et al. The morphological changes of monocytes in peripheral blood as a potential indicator for predicting active pulmonary tuberculosis[J]. Clinica Chimica Acta, 2018,481:189-192.
2
Castaño D, Barrera LF, Rojas M. Mycobacterium tuberculosis alters the differentiation of monocytes into macrophages in vitro [J]. Cell Immunol, 2011,268(2):60-67.
3
Weiss G, Schaible, UE. Macrophage defense mechanisms against intracellular bacteria [J]. Immunol Rev, 2015,264 (1):182-203.
4
吴雪琼,吴长有,梁艳,等.结核病免疫学[M].1版.北京:人民卫生出版社, 2016:94-97.
5
徐海亮,冯喜英,王玉清,等.肺结核患者多种相关免疫细胞因子的研究进展[J].中华肺部疾病杂志(电子版), 2017,10(2):220-222.
6
Nausch N, Lundtoft C, Schulz G, et al. Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis[J]. Int J Tuberc Lung Dis, 2017,21(3):270-277.
7
Wu J, Wang S, Lu C, et al. Multiple cytokine responses in discrimin-ating between active tuberculosis and latent tuberculosis infection[J].Tuberculosis(Edinb), 2017,102:68-75.
8
陈兴年,刘奇栋,王泓,等.活动性肺结核患者血清中白细胞介素6、8和肿瘤坏死因子α检测的临床意义[J].中国防痨杂志, 2015,37(4):344-347.
9
陈灏珠,钟南山,陆再英,等.内科学[M].8版.北京:人民卫生出版社, 2013:61-418.
10
万春辉,杜先智.维生素D诱导自噬对巨噬细胞清除结核分枝杆菌的作用[J].中国免疫学杂志, 2015,3(14): 256-261.
11
Shen P, Li Q, Ma J, et al. IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis[J]. BMC Microbiol, 2017,17(1):185.
12
Monin L, Khader SA. Chemokines in tuberculosis: the good,the bad and the ugly[J]. Semin Immunol, 2014,26(6):552-558.
13
Shrivastava P, Bagchi T. Differential expression of alpha II spectrin in monocytes of tuberculosis patients[J]. nt Immunopharmaacol,2013,17(3):759-762.
14
李继翰,曹新瑞.外周血内IL-37,IL8 ,IL-6水平与活动性肺结核患者病情的相关性[J].热带医学杂志, 2017,17(10):1389-1392.
15
李红,唐神结.肺结核患者外周血sIL-2R、TNF-α、IFN-γ、IL-6的检测及意义[J].中国防痨杂志, 2011,33(1):57-60.
16
Mishra BB, Moura-Alves P, Sonawane A, et al. Mycobacterium-tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome [J]. Cell Microbiol, 2010,12(8):1046-1063.
17
Mayer-Barber KD, Andrade BB, Barber DL, et al. Innate and adaptive interferons suppress IL-1α and IL-1β production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection [J]. Immunity, 2011,35(6):1023-1034.
18
张国良,王玲玲,詹森林,等.不同中医证型肺结核患者外周血CD14+单核细胞IL-1β、IL-1Ra表达水平的差异[J].环球中医药, 2016,9(10):1170-1174.
19
Jayaraman P, Sada-Ovalle I, Nishimura T, et al. IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation [J]. J Immunol, 2013,190 (8):4196-204.
20
李传友,刘忠泉,李卫民,等.脂多糖对感染卡介苗巨噬细胞表达细胞因子影响的研究[J].中国防痨杂志, 2004,26(3):133-135.
21
陶昆,卢贤瑜.肿瘤坏死因子-α抗结核免疫作用研究进展[J].国际检验医学杂志, 2006,27(2):143-145
22
Dey B, Bishai WR. Crosstalk between Mycobacterium tuberculosis and the host cell[J]. Semin Immunol, 2014,26(6):486-496.
[1] 李文金, 薛庆云. 白细胞介素家族炎性细胞因子在骨关节炎中的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(03): 348-353.
[2] 陈腊青, 林佳佳, 毛洪刚, 童冠海, 汪梦娜, 夏红波, 刘卓, 徐海霞, 赵玉华, 张传领. 血清细胞因子及呼出气一氧化氮在哮喘-慢性阻塞性肺疾病重叠综合征中的临床意义[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 316-320.
[3] 娄丽丽, 刘瀚旻. 儿童狼疮性肾炎相关肾小管间质损伤的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 373-378.
[4] 邬龙海, 黄淼, 龚云辉, 喻云倩. 血清趋化因子在妊娠期糖尿病孕妇中的临床价值[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 357-362.
[5] 闫凯悦, 邓慧玲, 张玉凤, 席淼, 李雨欣. 单核细胞趋化蛋白-1在感染性疾病中研究进展[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(04): 217-221.
[6] 王迎迎, 谢平. 乙型肝炎病毒感染合并肺结核患者发生肝损伤的危险因素及预测模型构建[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(04): 267-273.
[7] 李永浩, 高雪菲, 郭田田, 张进, 张彩针, 刘静. 肥胖合并甲状腺癌相关机制的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(04): 311-315.
[8] 孟原竹, 蒋国路, 陈小兵, 蒋莉. 肺结核合并侵袭性肺曲霉感染临床特征及危险因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 541-543.
[9] 肖泽林, 高健齐, 刘家杰, 曾定科. 负压封闭引流术治疗胸壁结核的临床应用[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 397-399.
[10] 沃吟晴, 杨向群. 心脏巨噬细胞的生理功能及在心肌梗死后的作用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 167-171.
[11] 王丽媛, 张瑞芳, 王向托, 王雅霄. 老年高尿酸血症患者血清白细胞介素-23、尿酸、单核细胞趋化蛋白-1与肾功能损伤的相关性研究[J]. 中华肾病研究电子杂志, 2023, 12(03): 145-149.
[12] 陈蕊, 杨洪娜, 方巍, 李鑫鑫, 李甜甜, 于孝义, 王艳雪, 李文玉. 血清与支气管肺泡灌洗液中细胞因子水平与肺内外ARDS的相关性研究[J]. 中华重症医学电子杂志, 2023, 09(03): 251-258.
[13] 刘立业, 赵德芳. 非酒精性脂肪肝患者血清细胞因子信号转导抑制因子3、肝X受体α水平与CT影像学特征的相关性[J]. 中华消化病与影像杂志(电子版), 2023, 13(04): 211-215.
[14] 郭文秀, 吴胜男, 王小芸, 张敏. 基于网络药理学的百部联合川贝母治疗肺结核的作用机制研究[J]. 中华临床医师杂志(电子版), 2023, 17(03): 335-342.
[15] 刘玉苓, 王婷婷, 吴高峰, 俞淑静. 健康体检人群内脏脂肪面积与新型炎症标志物的相关性研究[J]. 中华肥胖与代谢病电子杂志, 2023, 09(03): 197-202.
阅读次数
全文


摘要