γ-干扰素诱导蛋白-10 mRNA检测技术对结核病辅助诊断的价值

doi:10.19982/j.issn.1000-6621.20220518

中国防痨杂志 ›› 2023, Vol. 45 ›› Issue (5): 471-476.doi: 10.19982/j.issn.1000-6621.20220518

γ-干扰素诱导蛋白-10 mRNA检测技术对结核病辅助诊断的价值

宋瑞雪(), 魏荣荣, 董静, 贾红彦, 杜博平, 孙琦, 邢爱英, 李自慧, 朱传智, 张宗德, 潘丽萍()

耐药结核病研究北京市重点实验室/首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所, 北京 101149

收稿日期:2023-01-09 出版日期:2023-05-10 发布日期:2023-04-25
通信作者: 宋瑞雪,魏荣荣,潘丽萍 E-mail:panliping2006@163.com
基金资助:
通州区科技计划项目(KJ2022CX042);国家自然科学基金(82172279);国家自然科学基金(82070012);北京市自然科学基金(7192038);北京市自然科学基金(7212012);通州区运河计划人才项目(YH201807);通州区运河计划人才项目(YH202001);北京市医院管理中心青年职工创新工作室-创新梦工场(202136)

The performance of interferon gamma-induced protein 10 mRNA detection technology in auxiliary diagnosis of tuberculosis

Song Ruixue(), Wei Rongrong, Dong Jing, Jia Hongyan, Du Boping, Sun Qi, Xing Aiying, Li Zihui, Zhu Chuanzhi, Zhang Zongde, Pan Liping()

Beijing Key Laboratory for Drug Resistant Tuberculosis Research/Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China

Received:2023-01-09 Online:2023-05-10 Published:2023-04-25
Contact: Song Ruixue,Wei Rongrong,Pan Liping E-mail:panliping2006@163.com
Supported by:
Tongzhou Science and Technology Project(KJ2022CX042);National Natural Science Foundation of China(82172279);National Natural Science Foundation of China(82070012);Beijing Natural Science Foundation(7192038);Beijing Natural Science Foundation(7212012);Tongzhou Yunhe Project(YH201807);Tongzhou Yunhe Project(YH202001);Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support(202136)

摘要/Abstract

摘要： 目的评估以γ-干扰素诱导蛋白-10(interferon gamma-induced protein 10,IP-10)为靶标的检测技术(IP-10.TB)在结核病辅助诊断中的价值,并对比分析该检测技术与全血γ-干扰素释放试验(Quantiferon-TB Gold InTube,QFT-GIT)检测技术的一致性。方法于2021年11月至2022年7月,在首都医科大学附属北京胸科医院连续性、前瞻性纳入疑似结核病患者作为研究对象,最终纳入158例。根据研究对象的临床表现、常规生化检测、结核病病原学检测、影像学检测和(或)病理学检测结果,将其分为确诊结核病组(88例)、临床诊断结核病组(29例)和非结核病组(41例)。所有研究对象同时行外周血IP-10.TB检测和QFT-GIT检测,采用受试者工作特征曲线分析两种检测技术的诊断价值,两种检测技术的一致性分析采用Kappa检验。结果 158例研究对象中,IP-10.TB检测不确定结果7例(4.4%),QFT-GIT检测不确定结果5例(3.2%),两者比较差异无统计学意义(χ²=0.346,P=0.556)。在146例检测有效研究对象中,IP-10.TB诊断结核病的敏感度和特异度分别为96.3%(95%CI:90.1%~98.8%)和64.1%(95%CI:47.2%~78.3%),QFT-GIT诊断结核病的敏感度和特异度分别为97.2%(95%CI:91.4%~99.3%)和64.1%(95%CI:47.2%~78.3%)。两种检测技术的总符合率为92.5%(95%CI:88.2%~96.8%),阳性符合率为95.0%(95%CI:91.0%~98.9%),阴性符合率为82.1%(95%CI:68.0%~96.3%);一致性检验Kappa值为0.760(95%CI:0.624~0.895,P<0.001)。结论 IP-10.TB检测具有与QFT-GIT检测一致的诊断效能,可应用于结核病的辅助诊断。

关键词: 结核, 干扰素类, 干扰素诱导剂, 诊断, 鉴别, 对比研究

Abstract:

Objective: To evaluate the performance of the interferon gamma-induced-protein 10 (IP-10) assay (IP-10.TB) in auxiliary diagnosis of tuberculosis (TB), and analyze the concordance between IP-10.TB assay and the whole blood interferon gamma release assay (QFT-GIT). Methods: Suspected TB patients were prospectively and consecutively recruited in Beijing Chest Hospital, Capital Medical University between November 2021 and July 2022. According to the clinical manifestations, routine biochemical examinations, histopathological, radiological and (or) etiological examinations, a total of 158 cases with conclusive diagnosis were finally included, and the subjects were divided into definite TB group (88 cases), clinically diagnosed TB group (29 cases) and non-TB group (41 cases). IP-10.TB and QFT-GIT assays were simultaneously performed on peripheral blood samples. The diagnostic performance of IP-10.TB and QFT-GIT were analyzed using the receiver operating characteristic curve. Accordance of IP-10.TB and QFT-GIT was analyzed by Cohen’s Kappa test. Results: Among the 158 participants, there were 7 cases (4.4%) with indeterminate results of IP-10.TB and 5 cases (3.2%) with indeterminate results of QFT-GIT, respectively. No significant difference was detected in the ratio of indeterminate results between IP-10.TB assay and QFT-GIT (χ²=0.346, P=0.556). The total sensitivity and specificity of IP-10.TB assay were 96.3% (95%CI: 90.1%-98.8%) and 64.1% (95%CI:47.2%-78.3%), respectively; while the total sensitivity and specificity of QFT-GIT assay were 97.2% (95%CI: 91.4%-99.3%) and 64.1% (95%CI: 47.2%-78.3%), respectively. The total concordance rate of these two methods was 92.5% (95%CI: 88.2%-96.8%), the positive concordance rate was 95.0% (95%CI: 91.0%-98.9%) and the negative concordance rate was 82.1% (95%CI: 68.0%-96.3%). The Cohen’s Kappa value was 0.760 (95%CI: 0.624-0.895, P<0.001) between IP-10.TB and QFT-GIT assays. Conclusion: These results showed that the performance of IP-10.TB was consistent with that of QFT-GIT for auxiliary diagnosis of TB.

Key words: Tuberculosis, Interferons, Interferon inducers, Diagnosis, differentiation, Comparative study

中图分类号:

R52
R825.2

宋瑞雪, 魏荣荣, 董静, 贾红彦, 杜博平, 孙琦, 邢爱英, 李自慧, 朱传智, 张宗德, 潘丽萍. γ-干扰素诱导蛋白-10 mRNA检测技术对结核病辅助诊断的价值[J]. 中国防痨杂志, 2023, 45(5): 471-476. doi: 10.19982/j.issn.1000-6621.20220518

Song Ruixue, Wei Rongrong, Dong Jing, Jia Hongyan, Du Boping, Sun Qi, Xing Aiying, Li Zihui, Zhu Chuanzhi, Zhang Zongde, Pan Liping. The performance of interferon gamma-induced protein 10 mRNA detection technology in auxiliary diagnosis of tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(5): 471-476. doi: 10.19982/j.issn.1000-6621.20220518

图/表 3

表1

图1

表2

参考文献 19

[1]	World Health Organization. Global Tuberculosis Report 2022. Geneva: World Health Organization, 2022.
[2]	Zellweger JP, Sotgiu G, Corradi M, et al. The diagnosis of latent tuberculosis infection (LTBI): currently available tests, future developments, and perspectives to eliminate tuberculosis (TB). Med Lav, 2020, 111(3): 170-183. doi:10.23749/mdl.v111i3.9983. doi: 10.23749/mdl.v111i3.9983 pmid: 32624559
[3]	中华人民共和国国家卫生和计划生育委员会.WS 288—2017 肺结核诊断. 2017-11-09.
[4]	Xia H, Wang X, Li F, et al. Diagnostic values of the Quanti-FERON-TB Gold In-tube assay carried out in China for diagnosing pulmonary tuberculosis. PLoS One, 2015, 10(4): e0121021. doi:10.1371/journal.pone.0121021. doi: 10.1371/journal.pone.0121021 URL
[5]	Du F, Xie L, Zhang Y, et al. Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis. Sci Rep, 2018, 8(1):5882. doi:10.1038/s41598-018-24285-3. doi: 10.1038/s41598-018-24285-3 pmid: 29651163
[6]	Ruhwald M, Aabye MG, Ravn P. IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions. Expert Rev Mol Diagn, 2012, 12(2):175-187. doi:10.1586/erm.11.97. doi: 10.1586/erm.11.97 pmid: 22369377
[7]	Qiu X, Tang Y, Yue Y, et al. Accuracy of interferon-γ-induced protein 10 for diagnosing latent tuberculosis infection: a systematic review and meta-analysis. Clin Microbiol Infect, 2019, 25(6):667-672. doi:10.1016/j.cmi.2018.12.006. doi: 10.1016/j.cmi.2018.12.006 URL
[8]	Blauenfeldt T, Heyckendorf J, Graff Jensen S, et al. Development of a one-step probe based molecular assay for rapid immunodiagnosis of infection with M.tuberculosis using dried blood spots. PLoS One, 2014, 9(9): e105628. doi:10.1371/journal.pone.0105628. doi: 10.1371/journal.pone.0105628 URL
[9]	Pan L, Huang M, Jia H, et al. Diagnostic Performance of a Novel CXCL10 mRNA Release Assay for Mycobacterium tuberculosis Infection. Front Microbiol, 2022, 13: 825413. doi:10.3389/fmicb.2022.825413. doi: 10.3389/fmicb.2022.825413 URL
[10]	Jabri H, Lakhdar N, El Khattabi W, et al. Diagnostic means for tuberculosis. Rev Pneumol Clin, 2016, 72(5): 320-325. doi:10.1016/j.pneumo.2016.06.003. doi: S0761-8417(16)30063-3 pmid: 27561975
[11]	Antonelli A, Ferrari SM, Giuggioli D, et al. Chemokine (C-X-C motif) ligand (CXCL) 10 in autoimmune diseases. Autoimmun Rev, 2014, 13(3):272-280. doi:10.1016/j.autrev.2013.10.010. doi: 10.1016/j.autrev.2013.10.010 URL
[12]	Luster AD, Ravetch JV. Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site. Mol Cell Biol, 1987, 7(10): 3723-3731. doi:10.1128/mcb.7.10.3723-3731.1987. doi: 10.1128/mcb.7.10.3723-3731.1987 pmid: 2824996
[13]	Tsuboi H, Wakamatsu E, Iizuka M, et al. Importance of serine 727 phosphorylated STAT1 in IFNγ-induced signaling and apoptosis of human salivary gland cells. Int J Rheum Dis, 2011, 14(1):86-91. doi:10.1111/j.1756-185X.2010.01575.x. doi: 10.1111/j.1756-185X.2010.01575.x URL
[14]	Petrone L, Vanini V, Chiacchio T, et al. Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection. Tuberculosis(Edinb), 2018, 111:147-153. doi:10.1016/j.tube.2018.06.005. doi: 10.1016/j.tube.2018.06.005
[15]	中国医学科学院病原生物学研究所, 中国疾病预防控制中心, 中国科学院地理科学与资源研究所. 全国结核分枝杆菌潜伏感染率估算专家共识. 中国防痨杂志, 2022, 44(1):4-8. doi:10.19982/j.issn.1000-6621.20210662. doi: 10.19982/j.issn.1000-6621.20210662
[16]	Gao L, Li X, Liu J, et al. Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis, 2017, 17(10): 1053-1061. doi:10.1016/S1473-3099(17)30402-4. doi: S1473-3099(17)30402-4 pmid: 28716677
[17]	Lamberti M, Uccello R, Monaco MGL, et al. Tuberculin skin test and Quantiferon test agreement and influencing factors in tuberculosis screening of healthcare workers: a systematic review and meta-analysis. J Occup Med Toxicol, 2015, 10: 2. doi:10.1186/s12995-015-0044-y. doi: 10.1186/s12995-015-0044-y pmid: 25670962
[18]	Aggarwal AN, Agarwal R, Gupta D, et al. Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis. J Clin Microbiol, 2015, 53(8): 2451-2459. doi:10.1128/JCM.00823-15. doi: 10.1128/JCM.00823-15 pmid: 25994163
[19]	Lu P, Chen X, Zhu LM, et al. Interferon-Gamma Release Assays for the Diagnosis of Tuberculosis: A Systematic Review and Meta-analysis. Lung, 2016, 194(3): 447-458. doi:10.1007/s00408-016-9872-5. doi: 10.1007/s00408-016-9872-5 pmid: 27039307

特征	确诊结核病组(88例)	临床诊断结核病组(29例)	非结核病组(41例)
年龄[岁,M(Q₁,Q₃)]	45(32,58)	37(29,56)	56(44,67)
性别[例(构成比,%)]
男性	64(72.7)	14(48.3)	24(58.5)
女性	24(27.3)	15(51.7)	17(41.5)
肺结核[例(构成比,%)]	85(96.6)	24(82.8)	-
肺外结核[例(构成比,%)]	3(3.4)	5(17.2)	-
骨关节结核	1(1.1)	1(3.4)	-
淋巴结结核	-	2(7.0)	-
泌尿生殖系统结核	1(1.1)	-	-
结核性脑膜炎	-	1(3.4)	-
支气管结核	1(1.1)	-	-
肠结核	-	1(3.4)	-
其他疾病[例(构成比,%)]
肺癌	-	-	13(31.7)
肺炎	-	-	22(53.7)
非结核分枝杆菌肺病	-	-	4(9.8)
其他	-	-	2(4.8)

检测技术	综合诊断(例)		敏感度 [%(95%CI)]	特异度 [%(95%CI)]	阴性预测值 [%(95%CI)]	阳性预测值 [%(95%CI)]	阴性似然比 (95%CI)	阳性似然比 (95%CI)
检测技术	结核病组 (107例)	非结核病组(39例)	敏感度 [%(95%CI)]	特异度 [%(95%CI)]	阴性预测值 [%(95%CI)]	阳性预测值 [%(95%CI)]	阴性似然比 (95%CI)	阳性似然比 (95%CI)
IP-10.TB			96.3(90.1~ 98.8)	64.1(47.2~ 78.3)	86.2(67.4~ 95.5)	88.0(80.4~ 93.1)	0.058(0.022~ 0.157)	2.682(1.760~ 4.086)
阳性	103	14
阴性	4	25
QFT-GIT			97.2(91.4~ 99.3)	64.1(47.2~ 78.3)	89.3(70.6~ 97.2)	88.1(80.6~ 93.1)	0.044(0.014~ 0.137)	2.708(1.778~ 4.123)
阳性	104	14
阴性	3	25
联合诊断			100.0(95.7~ 100.0)	59.0(42.2~ 74.0)	100.0(82.2~ 100.0)	87.0(79.4~ 92.1)	-	2.440(1.673~ 3.551)
阳性	107	16
阴性	0	23

γ-干扰素诱导蛋白-10 mRNA检测技术对结核病辅助诊断的价值

The performance of interferon gamma-induced protein 10 mRNA detection technology in auxiliary diagnosis of tuberculosis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 19

相关文章 15

编辑推荐

Metrics

本文评价

友情链接

[1]	廖艺璇, 方创森, 李燕明. 加强结核病非定点医疗机构能力建设提高结核病诊断水平[J]. 中国防痨杂志, 2023, 45(5): 437-441.
[2]	王大宽, 张彬, 刘自森, 段伟焘, 高磊. 基层结核病预防性治疗门诊建设的探索与展望[J]. 中国防痨杂志, 2023, 45(5): 442-445.
[3]	李姗姗, 王玉峰, 舒薇, 逄宇. 结核病实验室诊断技术研发新进展[J]. 中国防痨杂志, 2023, 45(5): 446-453.
[4]	舒薇, 刘宇红. 精进臻善惟实励新:世界卫生组织《2022年全球结核病报告》解读[J]. 中国防痨杂志, 2023, 45(5): 454-457.
[5]	夏辉, 赵雁林. 世界卫生组织《结核病实验室加强实用手册(2022更新)》解读及对加强我国结核病实验室网络建设的启示[J]. 中国防痨杂志, 2023, 45(5): 458-463.
[6]	史雨婷, 董静, 贾红彦, 朱传智, 杨斌, 李自慧, 孙琦, 杜博平, 邢爱英, 张宗德, 潘丽萍. miR-99a-5p在结核分枝杆菌感染宿主巨噬细胞中的免疫调控作用[J]. 中国防痨杂志, 2023, 45(5): 464-471.
[7]	李红娜, 毛昕, 徐碧宇, 吴晨阳, 董丽儒, 宋旭东. 常见原位病理染色技术诊断肺结核的临床价值研究[J]. 中国防痨杂志, 2023, 45(5): 477-482.
[8]	闫晓婧, 王庆枫, 杨扬, 初乃惠, 聂文娟. 支气管肺泡灌洗液纳米孔测序对涂片阴性肺结核诊断价值的验证性研究[J]. 中国防痨杂志, 2023, 45(5): 487-492.
[9]	张鑫, 刘涛, 史志国, 翟文廷, 陈玢, 刘伟. 舒更葡糖钠对老年肺结核患者肺叶切除术后罗库溴铵血药浓度及肌松恢复的影响[J]. 中国防痨杂志, 2023, 45(5): 493-498.
[10]	李翔, 杞敏, 姜建杰, 魏佳璐, 付旭文, 李海雯, 张乐. 颅内结核合并急性脑梗死的危险因素分析[J]. 中国防痨杂志, 2023, 45(5): 499-506.
[11]	美合日班·买买提, 买吾拉江·依马木, 卢冬梅, 郑彦玲, 张学良, 彭孝旺. 基于分布滞后非线性模型研究新疆疏附县气温对肺结核发病的影响[J]. 中国防痨杂志, 2023, 45(5): 507-513.
[12]	任飞林, 刘小琦, 金玫华, 孙秀秀. 季节性差分自回归滑动平均模型对肺结核发病情况的预测效果研究[J]. 中国防痨杂志, 2023, 45(5): 514-519.
[13]	杨军, 邓强, 彭冉东, 李军杰, 王雨榕, 杨海云, 杜健强. 脊柱结核兔模型的建立及研究进展[J]. 中国防痨杂志, 2023, 45(5): 520-525.
[14]	李翔, 付旭文, 魏佳璐, 干玮, 李海雯, 代敏, 和进堂. 精囊腺结核的MRI影像特征分析——附7例精囊腺结核MRI影像表现[J]. 中国防痨杂志, 2023, 45(5): 526-530.
[15]	赵爱华, 都伟欣, 王国治, 徐苗. 重组结核分枝杆菌变态反应原皮肤试验用制剂命名探讨[J]. 中国防痨杂志, 2023, 45(4): 333-335.