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Screening and evaluation of Mycobacterium tuberculosis diagnostic antigens.
European Journal of Clinical Microbiology & Infectious Diseases ( IF 3.7 ) Pub Date : 2020-06-16 , DOI: 10.1007/s10096-020-03951-3
Zhongchen Ma 1 , Xiang Ji 2 , Hang Yang 1 , Jinke He 2 , Qian Zhang 3 , Yong Wang 1 , Zhen Wang 1 , Chuangfu Chen 1
Affiliation  

In recent years, the prevalence of tuberculosis worldwide has increased, and with it, the number of drug-resistant tuberculosis strains. This has brought new challenges towards prevention and control of the disease. Therefore, it is urgent to find reliable and rapid diagnostic methods for tuberculosis in general, and for the drug-resistant forms of the disease. To this aim, we assessed 17 tuberculosis-specific protein candidates for the detection of tuberculosis-specific antibodies. First, we established an indirect ELISA method to detect anti-Mycobacterium tuberculosis IgM and IgG. We tested 453 sera and analyzed the efficacy of the protein candidates for diagnosis of tuberculosis. Next, we screened antigens rich in T cell epitopes for their ability to induce high levels of IFN-γ, in order to define their suitability does develop detection tests based on IFN-γ release assay (IGRAs). The antigens CFP-10, PPE57, 38kDa, and Rv3807 showed higher diagnostic potential for the detection of anti-tuberculosis IgM, whereas PPE57, Ag85B, CFP-10, Rv0220, and 38kDa antigens performed better for anti-tuberculosis IgG detection. Worth noting is that CFP-10, 38kDa, and PPE57 detected efficiently both IgM and IgG. Rv1987, Rv3807, PPE57, Rv0220, and MPT64 proteins alone and combinations of Rv1987 + Rv3807, 16kDa + Rv0220, and MPT64 + Rv1986 tested in IGRAs displayed a good correlation with the positive control constituted by a cocktail of ESAT-6 + CFP-10 + TB7.7 (ECT), known for their stimulating properties (r > 0.5, p < 0.01). Among these antigen candidates, Rv0220 and Rv1987 + Rv3807 were the most potent. We discovered CFP-10, 38kDa, and PPE57 for the detection of anti-M. tuberculosis IgM and IgG, and Rv0220 alone or the combination Rv1987 + Rv3807 as the strongest stimulators in IGRAs. These antigens provide new references for the screening of tuberculosis-specific antibodies and effective stimulation in IGRAs.



中文翻译:

结核分枝杆菌诊断抗原的筛选和评估。

近年来,全世界结核病的患病率都有所增加,耐药结核病菌株的数量也随之增加。这给疾病的预防和控制带来了新的挑战。因此,迫切需要找到一种可靠且快速的诊断方法,以用于一般的结核病以及该病的耐药形式。为此,我们评估了17种结核特异性蛋白候选物,以检测结核特异性抗体。首先,我们建立了一种间接ELISA方法来检测抗结核分枝杆菌IgM和IgG。我们测试了453份血清,并分析了候选蛋白质对结核病诊断的功效。接下来,我们筛选了富含T细胞表位的抗原诱导高水平IFN-γ的能力,以定义其适用性,并根据IFN-γ释放测定法(IGRA)开展了检测测试。抗原CFP-10,PPE57、38kDa和Rv3807显示出更高的诊断潜力,可用于检测抗结核IgM,而PPE57,Ag85B,CFP-10,Rv0220和38kDa抗原在检测抗结核IgG方面表现更好。值得注意的是,CFP-10、38kDa和PPE57可以有效检测IgM和IgG。单独的Rv1987,Rv3807,PPE57,Rv0220和MPT64蛋白以及Rv1987 + Rv3807、16kDa + Rv0220的组合,r  > 0.5,p  <0.01)。在这些抗原候选物中,Rv0220和Rv1987 + Rv3807最​​有效。我们发现CFP-10、38kDa和PPE57可用于检测抗结核分枝杆菌IgM和IgG,以及单独的Rv0220或Rv1987 + Rv3807组合是IGRA中最强的刺激物。这些抗原为筛选结核特异性抗体和在IGRA中有效刺激提供了新的参考。

更新日期:2020-06-16
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