Nature:肺结核的生物标记

2010-08-19 00:00 · moon

对结核杆菌的免疫反应是复杂的,没有被完全定性,从而妨碍了新的诊断方法、治疗方法及疫苗的开发。现在,一种系统生物学方法被用来比较患有活性和休眠结核的患者与健康对照组所表达基因的转录谱。活性肺病被发现与一种由嗜中性细胞驱动的、干扰素可诱导的基因谱关联。 休眠结核患者约有10%会继续发

对结核杆菌的免疫反应是复杂的,没有被完全定性,从而妨碍了新的诊断方法、治疗方法及疫苗的开发。现在,一种系统生物学方法被用来比较患有活性和休眠结核的患者与健康对照组所表达基因的转录谱。活性肺病被发现与一种由嗜中性细胞驱动的、干扰素可诱导的基因谱关联。

休眠结核患者约有10%会继续发展成活性结核。在这项研究中,10%的休眠结核患者具有与活性结核患者相似的一个转录特征,说明该生物标记在预后和诊断中都可能是有用的。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature doi:10.1038/nature09247

An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

Matthew P. R. Berry,Christine M. Graham,Finlay W. McNab,Zhaohui Xu,Susannah A. A. Bloch,Tolu Oni,Katalin A. Wilkinson,Romain Banchereau,Jason Skinner,Robert J. Wilkinson,Charles Quinn,Derek Blankenship,Ranju Dhawan,John J. Cush,Asuncion Mejias,Octavio Ramilo,Onn M. Kon,Virginia Pascual,Jacques Banchereau,Damien Chaussabel" Anne O’Garra

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment1, 2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines4, 5. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and type I IFN-αβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-αβ signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.

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