Common patterns and disease-related signatures in tuberculosis and sarcoidosis
Common patterns and disease-related signatures in tuberculosis and sarcoidosis
复制标题
DOI：
10.1073/pnas.1121072109
复制
发表时间：
2012-05-15
影响因子：
11.1
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
--
作者：
Maertzdorf, Jeroen;Weiner, January, III;Kaufmann, Stefan H. E.
鉴于结核病 (TB) 对全球健康的显着影响，识别生物特征一直是人们关注的重点。迄今为止确定的血细胞中的基因表达谱表明活动性结核病中免疫系统的持续激活和慢性炎症病理。定义对结核病具有独特特异性的生物印记需要确定的特征可以区分具有相似病理学的疾病，例如结节病（SARC）。在这里，我们对肺结核和 SARC 进行了详细比较，包括全血基因表达谱、microRNA 表达和多重血清分析物。我们的分析表明，先前披露的结核病基因表达特征在 SARC 中表现出高度相似的模式，促炎途径和干扰素信号传导均上调，并且与结核病相关特征非常相似。两种疾病中的 microRNA 表达也呈现出高度相似的模式，而与 SARC 和对照组相比，结核病患者血清中的细胞因子显示出略微升高的促炎模式。我们的结果表明，这两种疾病之间的表达存在一些差异，结核病中的代谢活性增加，抗菌防御反应显着更高。然而，基质金属肽酶 14 被确定为 SARC 最独特的标记。两种不同的炎症性肺部疾病的血液特征中所描述的共性以及独特的特征不仅对结核病生物特征的设计和未来的诊断具有重要意义，而且还为不同病因的慢性炎症性疾病实体的生物过程提供了见解。
In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, witha common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.