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利用多种生物标志物反应区分潜伏性和活动性结核病。

Discriminating between latent and active tuberculosis with multiple biomarker responses.

机构信息

Center for AIDS Research, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Tuberculosis (Edinb). 2011 May;91(3):250-6. doi: 10.1016/j.tube.2011.02.006. Epub 2011 Mar 10.

DOI:10.1016/j.tube.2011.02.006
PMID:21393062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3090479/
Abstract

We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), latent tuberculosis (N = 32), or no evidence of tuberculosis infection (N = 26) were evaluated. We used the Luminex Multiplexed Bead Array platform to simultaneously evaluate 25 biomarkers in the supernatant of whole blood samples following overnight stimulation using the Quantiferon(®) Gold In-Tube kit. We defined the response to stimulation as the difference (within an individual patient) between the response to the pooled tuberculosis antigens and the negative control. IP-10 response was significantly higher in tuberculosis-infected (active or latent) subjects compared to the uninfected group (p < 0.0001). Among the 25 parameters, expression levels of IL-15 and MCP-1 were found to be significantly higher in the active tuberculosis group compared to the latent tuberculosis group (p = 0.0006 and 0.0030, respectively). When combined, IL-15 and MCP-1 accurately identified 83% of active and 88% of latent infections. The combination of IL-15 and MCP-1 responses was accurate in distinguishing persons with active tuberculosis from persons with latent tuberculosis in this study.

摘要

我们试图确定对结核分枝杆菌特异抗原的生物标志物反应,这些反应能够 1)改善结核感染的诊断,2)区分活动性和潜伏性感染。我们评估了 70 名活动性肺结核(N=12)、潜伏性肺结核(N=32)或无结核感染证据(N=26)的受试者。我们使用 Luminex 多重珠粒阵列平台,在使用 Quantiferon(®)金管试剂盒过夜刺激后,同时评估全血样本上清液中的 25 种生物标志物。我们将刺激反应定义为个体内对 pooled tuberculosis 抗原的反应与阴性对照之间的差异。与未感染组相比,感染结核分枝杆菌(活动性或潜伏性)的受试者的 IP-10 反应明显更高(p<0.0001)。在 25 个参数中,IL-15 和 MCP-1 的表达水平在活动性肺结核组中明显高于潜伏性肺结核组(p=0.0006 和 0.0030)。联合使用时,IL-15 和 MCP-1 可准确识别 83%的活动性感染和 88%的潜伏性感染。在这项研究中,IL-15 和 MCP-1 反应的组合可准确区分活动性肺结核患者和潜伏性肺结核患者。

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本文引用的文献

1
Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons?IP-10 是否是 HIV 感染者中检测结核分枝杆菌特异性反应的准确标志物?
PLoS One. 2010 Sep 7;5(9):e12577. doi: 10.1371/journal.pone.0012577.
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Decay kinetics of an interferon gamma release assay with anti-tuberculosis therapy in newly diagnosed tuberculosis cases.新诊断结核病病例中抗结核治疗对干扰素γ释放试验的衰减动力学。
PLoS One. 2010 Sep 1;5(9):e12502. doi: 10.1371/journal.pone.0012502.
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Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.MCP-1 基因型 GG 和 MMP-1 基因型 2G/2G 的联合作用增加了卡介苗接种者发生肺结核的可能性。
PLoS One. 2010 Jan 25;5(1):e8881. doi: 10.1371/journal.pone.0008881.
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Tuberculosis treatment effect on T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens.结核分枝杆菌特异性抗原刺激的 T 细胞干扰素-γ反应对结核病治疗效果的影响。
Eur Respir J. 2010 Aug;36(2):355-61. doi: 10.1183/09031936.00151309. Epub 2009 Nov 19.
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Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls.检测白细胞介素-2 加上干扰素-γ可区分活动性肺结核患者、潜伏性感染者和对照者。
Clin Microbiol Infect. 2010 Aug;16(8):1282-4. doi: 10.1111/j.1469-0691.2009.03104.x. Epub 2009 Nov 2.
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Usefulness of interferon-gamma release assays for diagnosing TB infection and problems with these assays.γ-干扰素释放试验在诊断结核感染中的应用价值及这些试验存在的问题。
J Infect Chemother. 2009 Jun;15(3):143-55. doi: 10.1007/s10156-009-0686-8. Epub 2009 Jun 25.
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Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.全血γ-干扰素释放试验上清液中的宿主标志物可区分活动性结核病与潜伏性结核感染:初步报告
BMC Pulm Med. 2009 May 16;9:21. doi: 10.1186/1471-2466-9-21.
8
IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay.在基于全血的T细胞检测中,IP-10、MCP-1、MCP-2、MCP-3和IL-1RA有望作为结核分枝杆菌感染的生物标志物。
BMC Res Notes. 2009 Feb 4;2:19. doi: 10.1186/1756-0500-2-19.
9
IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway.白细胞介素-15将Toll样受体2/1诱导的巨噬细胞分化与维生素D依赖性抗菌途径联系起来。
J Immunol. 2008 Nov 15;181(10):7115-20. doi: 10.4049/jimmunol.181.10.7115.
10
MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa.MCP-1启动子变体-362C与西非加纳的肺结核防护相关。
Hum Mol Genet. 2009 Jan 15;18(2):381-8. doi: 10.1093/hmg/ddn352. Epub 2008 Oct 20.