Novel biomarkers distinguishing active tuberculosis from latent infection identified by gene expression profile of peripheral blood mononuclear cells.
Novel biomarkers distinguishing active tuberculosis from latent infection identified by gene expression profile of peripheral blood mononuclear cells.
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通过外周血单核细胞基因表达谱鉴定区分活动性结核病和潜伏感染的新型生物标志物
DOI：
10.1371/journal.pone.0024290
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Lu C;Wu J;Wang H;Wang S;Diao N;Wang F;Gao Y;Chen J;Shao L;Weng X;Zhang Y;Zhang W
人类感染结核分枝杆菌（MTB）后，可以消除病原体，或者变成潜伏感染或活动性疾病。然而，影响病原体清除和潜伏感染的疾病进展的因素知之甚少。本研究试图使用全基因组转录组方法来鉴定与MTB感染相关的免疫因子和可以区分活动性疾病与潜伏性感染的新型生物标志物。方法/主要发现使用微阵列分析，我们全面确定了12个个体中纯化蛋白衍生物（PPD）刺激的外周血单核细胞（PBMC）的转录差异，这些个体被分为三组：TB患者（TB）、潜伏性TB感染个体（LTBI）和健康对照（HC）（每组n=4）。 506个差异表达基因的转录谱可以正确地将研究个体分为三个簇。此外，分别鉴定了结核病感染（TB<BI）和活动性疾病（TB）的55个和229个转录物标签。在83个个体中进行的定量实时PCR（qPCR）验证研究证实了81%的微阵列鉴定基因的表达模式。决策树分析表明，CXCL 10、ATP 10A和TLR 6三个基因可以区分TB和LTBI。进行额外的验证以评估36名受试者中三种生物标志物的诊断能力，其灵敏度为71%，特异性为89%。PPD诱导的PBMC的转录谱鉴定了与不同感染状态相关的独特基因表达模式，并为人类对MTB的免疫应答提供了新的见解。此外，本研究表明，CXCL 10，ATP 10A和TLR 6的组合可以用作区分TB和LTBI的新生物标志物。
Background Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection. Methodology/Principal Findings Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB<BI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%. Conclusions/Significance The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI.
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影响因子：
82.9
作者：
Harari A;Rozot V;Bellutti Enders F;Perreau M;Stalder JM;Nicod LP;Cavassini M;Calandra T;Blanchet CL;Jaton K;Faouzi M;Day CL;Hanekom WA;Bart PA;Pantaleo G
通讯作者：
Pantaleo G
DOI：
10.1186/1476-9433-1-2
发表时间：
2002-11-18
期刊：
Medical immunology (London, England)
影响因子：
--
作者：
Beadling, Carol;Smith, Kendall A
通讯作者：
Smith, Kendall A
DOI：
10.1007/s10096-008-0670-8
发表时间：
2009-06-01
影响因子：
4.5
作者：
Chee, C. B. E.;Barkham, T. M. S.;Wang, Y. T.
通讯作者：
Wang, Y. T.
DOI：
10.1111/j.1440-1843.2010.01739.x
发表时间：
2010-04
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Dheda K;Schwander SK;Zhu B;van Zyl-Smit RN;Zhang Y
通讯作者：
Zhang Y
影响因子：
64.8
作者：
通讯作者：
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