论著
ENGLISH ABSTRACT
FCGR1B基因转录水平检测对活动性结核病诊断的价值研究
刘艳华
王若
安红娟
程小星
作者及单位信息
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DOI: 10.3760/cma.j.cn112147-20211213-00878
Diagnostic value of FCGR1B gene transcription level in active tuberculosis
Liu Yanhua
Wang Ruo
An Hongjuan
Cheng Xiaoxing
Authors Info & Affiliations
Liu Yanhua
Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing 100091, China
Wang Ruo
Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing 100091, China
An Hongjuan
Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing 100091, China
Cheng Xiaoxing
Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing 100091, China
·
DOI: 10.3760/cma.j.cn112147-20211213-00878
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摘要

目的研究免疫球蛋白γFc段受体1b(Fc fragment of IgG receptor 1b, FCGR1B)基因转录水平检测对活动性结核病的诊断价值。

方法2018年2—9月,收集解放军总医院第八医学中心活动性结核病患者、结核潜伏感染者(LTBI)、治愈结核病患者、健康人和肺炎患者的外周血,分离外周血单个核细胞(PBMC),提取总RNA并反转录为cDNA,实时荧光定量聚合酶链式反应(QPCR)检测PBMC中 FCGR1B基因mRNA的相对表达量,非参数检验比较活动性结核病和对照组 FCGR1B基因mRNA的表达差异、相关性分析 FCGR1B基因mRNA的表达与结核病病情和感染指标的关系,受试者工作特征曲线(ROC)评估 FCGR1B基因转录水平检测在活动性结核病诊断中的价值。

结果与非结核组(包括LTBI、健康人、治愈结核和肺炎患者)相比,活动性结核病患者PBMC中 FCGR1B基因mRNA的表达较高( u=2081, P<0.001);结核患者的载菌量越多, FCGR1B基因mRNA的表达越高( H=12.35, P=0.015),与C反应蛋白(CRP)的表达显著相关( r=0.30, P=0.008); FCGR1B基因mRNA鉴别活动性结核病的曲线下面积(AUC)为0.849,诊断的敏感度和特异度分别为71.43%和84.17%, FCGR1B基因mRNA鉴别肺外结核的AUC为0.906,诊断的敏感度和特异度分别为84.62%和91.89%。

结论 FCGR1B基因mRNA是潜在的活动性结核病分子诊断标志物。

mRNA;活动性结核;诊断标志物; FCGR1B基因
ABSTRACT

ObjectiveTo investigate the diagnostic potential of Fc fragment of IgG receptor 1b gene ( FCGR1B) transcription level in active tuberculosis.

MethodsFrom February to September of 2018, we collected peripheral blood from patients with active tuberculosis, latent tuberculosis infection (LTBI), cured patients with tuberculosis, healthy people and patients with pneumonia in the Eighth Medical Center of PLA General Hospital. Peripheral blood mononuclear cells (PBMCs) were isolated for total RNA extraction and cDNA synthesis. The expression of FCGR1B mRNA in PBMCs was detected by quantitative real-time PCR (QPCR). Nonparametric test was used to compare the differential expression of FCGR1B mRNA between patients with active tuberculosis and control groups, and the relationships between FCGR1B mRNA expression and patient′s illness condition and inflammatory indexes were analyzed by Correlation analysis. The potential of FCGR1B mRNA as a diagnostic marker for active tuberculosis was evaluated by receiver operating characteristic curve (ROC) analysis.

ResultsThe expression of FCGR1B mRNA in PBMCs from patients with active tuberculosis was significantly increased when compared with non-tuberculosis controls, including individuals with LTBI, healthy people, cured patients with tuberculosis and patients with pneumonia ( u=2 081, P<0.001). The expression of FCGR1B mRNA was higher in patients with tuberculosis who had more bacteria( H=12.35, P=0.015), and was correlated with the C-reactive protein (CRP) ( r=0.30, P=0.008). ROC analysis showed that FCGR1B mRNA could distinguish active tuberculosis from non-tuberculosis with area under curve (AUC) of 0.849. The sensitivity and specificity were 71.43% and 84.17% respectively. The AUC of FCGR1B mRNA in distinguishing extra-pulmonary tuberculosis from controls was 0.906. The sensitivity and specificity were 84.62% and 91.89%, respectively.

Conclusion FCGR1B mRNA is a potential molecular marker for diagnosis of active tuberculosis.

mRNA;Active tuberculosis;Diagnostic markers; FCGR1B
Cheng Xiaoxing, Email: mocdef.3ab61nc63cx
引用本文

刘艳华,王若,安红娟,等. FCGR1B基因转录水平检测对活动性结核病诊断的价值研究 [J]. 中华结核和呼吸杂志,2022,45(04):373-378.

DOI:10.3760/cma.j.cn112147-20211213-00878

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结核病是由结核分枝杆菌( Mycobacterium tuberculosis,MTB)感染引起的慢性传染病,是全球十大死因之一,也是世界上单一传染病中的头号杀手,严重威胁着人类的健康。世界卫生组织(WHO)报道2019年全球新发结核患者1 000万例,死亡140万例。2019年我国新发结核患者83万例,死亡3万多例 1
2014年WHO提出了“终结结核病”的目标,即到2035年结核病发病率降至2015年的10%,病死率降至2015年的5%左右,实现这一目标的关键是提高结核病的诊断水平 2。目前结核病常用的实验室诊断方法包括涂片、细菌培养、核酸检测、结核抗体检测、γ-干扰素释放试验(interfron-gamma release assay,IGRA)和病理学诊断等。但是即便有这么多方法,结核病的诊断仍然是结核病防治中的难点,临床经常会出现误诊和漏诊的情况 3 , 4
近年来研究者们在评估差异表达基因作为活动性结核病诊断标志物方面做了许多工作 5 , 6 , 7 , 8 , 9。我们通过外周血单个核细胞(peripheral blood mononuclear cells,PBMC)转录组测序,筛选出活动性结核病患者与健康对照者差异表达基因,其中免疫球蛋白γFc段受体1b(Fc fragment of IgG receptor 1b, FCGR1B)基因是表达差异最显著的基因之一,在活动性结核病患者的表达显著高于对照组。 FCGR1B基因位于第一染色体上,编码高亲和力FCGR1B蛋白,该蛋白能与IgG的Fc区域结合,在体液免疫中发挥作用。有研究发现含 FCGR1B基因的多基因mRNA组合是潜在的活动性结核病诊断标志物 10 , 11。为了进一步分析 FCGR1B基因在结核病中的表达及其作为结核病诊断标志物的潜能,本研究利用荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,QPCR)检测了活动性结核病患者和对照人群PBMC中 FCGR1B基因mRNA的水平,评估了 FCGR1B基因转录水平检测在活动性结核病诊断中的价值。
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备注信息
A
程小星,Email: mocdef.3ab61nc63cx
B

刘艳华:设计实验、实施研究、分析数据、论文撰写、统计学分析;王若、安红娟:实施研究、采集数据;程小星:研究指导、论文审阅、经费支持

C

刘艳华, 王若, 安红娟, 等. FCGR1B基因转录水平检测对活动性结核病诊断的价值研究[J]. 中华结核和呼吸杂志, 2022, 45(4): 373-378. DOI: 10.3760/cma.j.cn112147-20211213-00878.

D
所有作者声明无利益冲突
E
艾滋病和病毒性肝炎等重大传染病防治专项 (2017ZX10201301-007-002)
国家自然科学基金 (82072233)
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