Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
Division of Immunology and Molecular Biology, LEPRA Society-Blue Peter Public Health and Research Center, Hyderabad, India.
PLoS One. 2018 Nov 26;13(11):e0207787. doi: 10.1371/journal.pone.0207787. eCollection 2018.
Latent tuberculosis infection (LTBI) is a clinically distinct category of Mycobacterium tuberculosis (Mtb) infection that needs to be diagnosed at the initial stage. We have reported earlier that one of the Mtb proline-proline-glutamic acid (PPE) proteins, PPE17 (Rv1168c) is associated with stronger B-cell and T-cell responses and could be used to diagnose different clinical categories of active TB patients with higher specificity and sensitivity than PPD and ESAT-6. Based on these observations we further tested the potential of PPE17 for the diagnosis of LTBI. We tested 198 sera samples collected from LTBI individuals (n = 61), QFT-negative (n = 58) and active TB patients (n = 79). Individuals were defined as LTBI by QuantiFERON-TB Gold In-Tube test (QFT-GIT) positive results, while active TB patients were confirmed based on the guidelines of the Revised National TB Control Programme of India. The antibody responses against PPE17, ESAT-6:CFP-10 and PPD were compared in these subjects by enzyme-linked immunosorbent assay. We observed that LTBI individuals show a higher sero-reactivity to PPE17 as compared to currently used latent TB diagnostic antigens like ESAT-6, CFP-10 and PPD. The LTBI and active TB patients display almost similar sensitivity. Interestingly, PPE17 could discriminate LTBI positive subjects from the QFT-negative subjects (P < 0.001). Our study hints that PPE17 may be used as a novel serodiagnostic marker to screen the latently infected subjects and may also be used as a complimentary tool to the QFT-GIT.
潜伏性结核感染（LTBI）是一种临床明显的结核分枝杆菌（Mtb）感染类别，需要在早期诊断。我们之前曾报道过，Mtb 脯氨酸-脯氨酸-谷氨酸（PPE）蛋白之一 PPE17（Rv1168c）与更强的 B 细胞和 T 细胞反应相关，并且可以用于诊断不同临床类别的活动性结核病患者，其特异性和敏感性均高于 PPD 和 ESAT-6。基于这些观察结果，我们进一步测试了 PPE17 用于诊断 LTBI 的潜力。我们测试了来自 LTBI 个体（n=61）、QFT 阴性（n=58）和活动性 TB 患者（n=79）的 198 份血清样本。LTBI 个体通过 QuantiFERON-TB Gold In-Tube 试验（QFT-GIT）阳性结果来定义，而活动性 TB 患者则根据印度修订国家结核病控制计划的指南来确认。通过酶联免疫吸附试验比较了这些受试者对 PPE17、ESAT-6:CFP-10 和 PPD 的抗体反应。我们观察到，与目前用于 LTBI 诊断的抗原 ESAT-6、CFP-10 和 PPD 相比，LTBI 个体对 PPE17 的血清反应性更高。LTBI 和活动性 TB 患者的敏感性几乎相似。有趣的是，PPE17 可以将 LTBI 阳性个体与 QFT 阴性个体区分开来（P<0.001）。我们的研究表明，PPE17 可能被用作筛查潜伏感染个体的新型血清诊断标志物，也可作为 QFT-GIT 的补充工具。
