Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis
Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis
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DOI：
10.1007/s00109-007-0157-6
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
--
作者：
Jacobsen, Marc;Repsilber, Dirk;Kaufmann, Stefan H. E.
结核分枝杆菌感染在约90%的感染者中通过有效的免疫反应得到控制，而不会发病。虽然已经确定了基本的保护介质，如干扰素- γ，但这些因素不足以预测结核分枝杆菌感染的结果。作为确定其他生物标志物的第一步，我们通过微阵列分析比较了结核病患者和感染结核分枝杆菌的健康供者外周血单个核细胞的基因表达谱。差异表达的候选基因主要来源于单核细胞，由参与抗微生物防御、炎症、趋化和细胞内运输的分子组成。我们通过定量聚合酶链反应分析验证了α -防御素1、α -防御素4、乳铁蛋白、Fc γ受体1A（分化簇64 [CD64]）、杀菌通透性增加蛋白和甲酰基肽受体1的差异表达。此外，我们在结核病患者的单核细胞中发现CD64蛋白表达增加。然后对候选生物标志物进行评估，以获得最佳的研究组区分。通过线性判别分析，由乳铁蛋白、CD64和ras相关的GTPase 33A组成的最小基因组足以对(1)结核病患者、(2)感染结核分枝杆菌的健康供者和(3)未感染的健康供者进行分类。
Infection with Mycobacterium tuberculosis is controlled by an efficacious immune response in about 90% of infected individuals who do not develop disease. Although essential mediators of protection, e.g., interferon-gamma, have been identified, these factors are insufficient to predict the outcome of M. tuberculosis infection. As a first step to determine additional biomarkers, we compared gene expression profiles of peripheral blood mononuclear cells from tuberculosis patients and M. tuberculosis-infected healthy donors by microarray analysis. Differentially expressed candidate genes were predominantly derived from monocytes and comprised molecules involved in the antimicrobial defense, inflammation, chemotaxis, and intracellular trafficking. We verified differential expression for alpha-defensin 1, alpha-defensin 4, lactoferrin, Fc gamma receptor 1A (cluster of differentiation 64 [CD64]), bactericidal permeability-increasing protein, and formyl peptide receptor 1 by quantitative polymerase chain reaction analysis. Moreover, we identified increased protein expression of CD64 on monocytes from tuberculosis patients. Candidate biomarkers were then assessed for optimal study group discrimination. Using a linear discriminant analysis, a minimal group of genes comprising lactoferrin, CD64, and the Ras-associated GTPase 33A was sufficient for classification of (1) tuberculosis patients, (2) M. tuberculosis-infected healthy donors, and (3) noninfected healthy donors.