Screening of highly expressed mycobacterial genes identifies Rv3615c as a useful differential diagnostic antigen for the Mycobacterium tuberculosis complex
Screening of highly expressed mycobacterial genes identifies Rv3615c as a useful differential diagnostic antigen for the Mycobacterium tuberculosis complex
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DOI：
10.1128/iai.00150-08
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发表时间：
2008-09-01
影响因子：
3.1
通讯作者：
Ewer, Katie
中科院分区：
文献类型：
--
作者：
Sidders, Ben;Pirson, Chris;Ewer, Katie
由分枝杆菌引起的真菌感染，特别是人和牛的结核病，在临床上和经济上都是重要的。人类可以接种卡介苗（BCG），目前正在积极考虑对牛采取包括接种疫苗在内的控制措施。然而，基于结核菌素的诊断试验不能区分真正的感染和接种卡介苗。因此，需要鉴定能够进行这种区分的鉴别诊断抗原，并且直到现在基于序列的方法一直占主导地位。在这里，我们探讨了抗原性和mRNA表达水平之间的联系，以及我们可能能够通过分析定量的全球转录谱来检测差异抗原的可能性。我们产生了14个候选抗原的列表，这些抗原在结核分枝杆菌和M。牛在各种生长条件下。这些候选人在M.牛感染和未感染牛刺激γ干扰素（IFN-γ）应答的能力。我们鉴定了一种抗原，Rv 3615 c，其在显著比例的M中刺激IFN-γ应答。感染牛（11/30头牛[37%] [P < 0.01]），但未感染或接种BCG的动物中未感染。重要的是，相同的抗原刺激IFN-γ应答的显着比例的感染牛，不响应于充分表征的分枝杆菌抗原ESAT-6和CFP-10。因此，Rv 3615 c表位与先前描述的基于ESAT-6和CFP-10的鉴别测试组合使用具有显著增加诊断灵敏度而不降低BCG接种人群中的特异性的潜力。
Tuberculous infections caused by mycobacteria, especially tuberculosis of humans and cattle, are important both clinically and economically. Human populations can be vaccinated with Mycobacterium bovis bacille Calmette-Guerin (BCG), and control measures for cattle involving vaccination are now being actively considered. However, diagnostic tests based on tuberculin cannot distinguish between genuine infection and vaccination with BCG. Therefore, identification of differential diagnostic antigens capable of making this distinction is required, and until now sequence-based approaches have been predominant. Here we explored the link between antigenicity and mRNA expression level, as well as the possibility that we may be able to detect differential antigens by analyzing quantified global transcriptional profiles. We generated a list of 14 candidate antigens that are highly expressed in Mycobacterium tuberculosis and M. bovis under a variety of growth conditions. These candidates were screened in M. bovis-infected and naive cattle for the ability to stimulate a gamma interferon (IFN-gamma) response. We identified one antigen, Rv3615c, which stimulated IFN-gamma responses in a significant proportion of M. bovis-infected cattle (11 of 30 cattle [37%] [P < 0.01]) but not in naive or BCG-vaccinated animals. Importantly, the same antigen stimulated IFN-gamma responses in a significant proportion of infected cattle that did not respond to the well-characterized mycobacterial antigens ESAT-6 and CFP-10. Therefore, use of the Rv3615c epitope in combination with previously described differential tests based on ESAT-6 and CFP-10 has the potential to significantly increase diagnostic sensitivity without reducing specificity in BCG-vaccinated populations.