针对结核分枝杆菌免疫蛋白质组学鉴定的人 T 细胞抗原的 IFN-γ/TNF-α 比值 - 潜伏性结核感染的最佳替代生物标志物。

IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection.

机构信息

Department of Immunology, National Institute for Research in Tuberculosis (ICMR), No. 1, Mayor Sathyamoorthy Road, Chetpet, Chennai 600 031, Tamil Nadu, India.

出版信息

J Infect. 2015 Aug;71(2):238-49. doi: 10.1016/j.jinf.2015.04.032. Epub 2015 Apr 29.

DOI:10.1016/j.jinf.2015.04.032

PMID:25936741

Abstract

The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-γ release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.

摘要

潜伏性结核感染（LTBI）巨大储存库对全球结核病控制构成重大障碍。现有的结核菌素皮肤试验（TST）和 IFN-γ 释放试验（IGRAs）被发现不适合 LTBI 诊断。之前，我们采用免疫蛋白质组学方法鉴定了 10 个蛋白片段（包含 16 个蛋白），这些蛋白片段仅被 LTBI 识别。在一组 40 例肺结核患者（PTB）和 35 名健康家庭接触者（HHC）中，通过使用 1:10 稀释全血检测法，针对 16 种抗原测量 IFN-γ 和 TNF-α 反应。在所有抗原中，Rv2626c 刺激的 IFN-γ 反应在 HHC 中的阳性率为 88.57%，而在 PTB 组中的阳性率为 7.5%。Rv2626c+Rv3716c 组合刺激的 IFN-γ 反应在 HHC 中的阳性率为 100%，而在 PTB 组中的阳性率为 17.5%。与单个细胞因子（即 IFN-γ 和 TNF-α）相比，IFN-γ/TNF-α 比值对 LTBI 的诊断具有良好的效果。针对 Rv3716c 和 TrxC 的 IFN-γ/TNF-α 比值在 HHC 中的阳性率为 94.29%，而在 PTB 组中的阳性率为 5%。Rv2626c 和 Rv3716c 的加入可能会提高现有 QFT-GIT 的诊断性能。与 QFT-GIT 检测法无关，针对 Rv3716c 或 TrxC 的 IFN-γ/TNF-α 比值可作为 LTBI 的合适替代生物标志物。