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对PPE蛋白Rv1168c的强烈免疫反应与活动性肺结核的关联。

Association of strong immune responses to PPE protein Rv1168c with active tuberculosis.

作者信息

Khan Nooruddin, Alam Kaiser, Nair Shiny, Valluri Vijaya Lakshmi, Murthy Kolluri J R, Mukhopadhyay Sangita

机构信息

Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Nacharam, Hyderabad 500076, Andhra Pradesh, India.

出版信息

Clin Vaccine Immunol. 2008 Jun;15(6):974-80. doi: 10.1128/CVI.00485-07. Epub 2008 Apr 9.

Abstract

Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients.

摘要

准确诊断结核感染对于结核病的治疗、预防和控制至关重要。基于纯蛋白衍生物(PPD)的传统诊断测试无法达到所需的诊断敏感性。因此,在本研究中,我们评估了PPE家族成员Rv1168c与结核菌素试验中常规使用的PPD以及结核分枝杆菌的著名免疫显性抗原Hsp60和ESAT-6相比的免疫原性。在传统的酶免疫测定中,重组Rv1168c蛋白对临床活动性结核病患者的血清显示出比PPD、Hsp60或ESAT-6更强的免疫反应性,并且可以将结核病患者与接种卡介苗的对照区分开来。有趣的是,Rv1168c抗原能够诊断涂片阴性肺结核以及肺外结核病例,而这些病例通常难以通过传统测试进行诊断。Rv1168c的免疫显性特性使其成为结核病血清诊断中一个有前途的候选物。此外,我们的研究还表明,Rv1168c是一种有效的T细胞抗原,可在从结核病患者获得的致敏外周血单核细胞中引发强烈的γ干扰素反应。

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