新型结核分枝杆菌感染相依赖抗原在高负担环境中结核病诊断中的应用潜力。

Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting.

机构信息

DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa.

出版信息

BMC Infect Dis. 2012 Jan 20;12:10. doi: 10.1186/1471-2334-12-10.

DOI:10.1186/1471-2334-12-10

PMID:22260319

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3282638/

Abstract

BACKGROUND

Confirming tuberculosis (TB) disease in suspects in resource limited settings is challenging and calls for the development of more suitable diagnostic tools. Different Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens may be differentially recognized in infected and diseased individuals and therefore useful as diagnostic tools for differentiating between M.tb infection states. In this study, we assessed the diagnostic potential of 118 different M.tb infection phase-dependent antigens in TB patients and household contacts (HHCs) in a high-burden setting.

METHODS

Antigens were evaluated using the 7-day whole blood culture technique in 23 pulmonary TB patients and in 19 to 21 HHCs (total n = 101), who were recruited from a high-TB incidence community in Cape Town, South Africa. Interferon-gamma (IFN-γ) levels in culture supernatants were determined by ELISA.

RESULTS

Eight classical TB vaccine candidate antigens, 51 DosR regulon encoded antigens, 23 TB reactivation antigens, 5 TB resuscitation promoting factors (rpfs), 6 starvation and 24 other stress response-associated TB antigens were evaluated in the study. The most promising antigens for ascertaining active TB were the rpfs (Rv0867c, Rv2389c, Rv2450c, Rv1009 and Rv1884c), with Areas under the receiver operating characteristics curves (AUCs) between 0.72 and 0.80. A combination of M.tb specific ESAT-6/CFP-10 fusion protein, Rv2624c and Rv0867c accurately predicted 73% of the TB patients and 80% of the non-TB cases after cross validation.

CONCLUSIONS

IFN-γ responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between M.tb infection states.

摘要

背景

在资源有限的环境中确诊结核病（TB）具有挑战性，需要开发更合适的诊断工具。不同的结核分枝杆菌（M.tb）感染阶段相关抗原在感染和患病个体中的识别可能存在差异，因此可作为区分 M.tb 感染状态的诊断工具。在这项研究中，我们评估了 118 种不同的 M.tb 感染阶段相关抗原在高负担环境中的肺结核患者和家庭接触者（HHC）中的诊断潜力。

方法

使用 7 天全血培养技术在 23 例肺结核患者和 19-21 例 HHC（共 101 例）中评估抗原，这些患者均来自南非开普敦一个高结核发病率的社区。通过 ELISA 测定培养上清液中的干扰素-γ（IFN-γ）水平。

结果

在这项研究中评估了 8 种经典的 TB 疫苗候选抗原、51 种 DosR 调控子编码抗原、23 种 TB 再激活抗原、5 种 TB 复苏促进因子（rpfs）、6 种饥饿和 24 种其他应激反应相关的 TB 抗原。确定活动性 TB 的最有前途的抗原是 rpfs（Rv0867c、Rv2389c、Rv2450c、Rv1009 和 Rv1884c），其受试者工作特征曲线下面积（AUCs）在 0.72 到 0.80 之间。经过交叉验证，M.tb 特异性 ESAT-6/CFP-10 融合蛋白、Rv2624c 和 Rv0867c 的组合可准确预测 73%的 TB 患者和 80%的非 TB 病例。