De Groote Mary Ann, Higgins Michael, Hraha Thomas, Wall Kirsten, Wilson Michael L, Sterling David G, Janjic Nebojsa, Reves Randall, Ochsner Urs A, Belknap Robert
SomaLogic, Inc., Boulder, Colorado, USA.
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
J Clin Microbiol. 2017 Feb;55(2):391-402. doi: 10.1128/JCM.01646-16. Epub 2016 Nov 16.
The tests for diagnosing latent tuberculosis infection (LTBI) are limited by a poor predictive value for identifying people at the highest risk for progressing to active tuberculosis (TB) and have various sensitivities and specificities in different populations. Identifying a more robust signature for LTBI is important for TB prevention and elimination. A pilot study was conducted with samples from immigrants to the United States that were screened for LTBI by the three commercially approved tests, namely, the tuberculin skin test (TST), the Quantiferon-TB Gold in-tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). QFT-GIT supernatants from 13 people with concordant positive results and 26 people with concordant negative results were analyzed via the highly multiplexed SOMAscan proteomic assay. The proteins in the stimulated supernatants that distinguished LTBI from controls included interleukin-2 (IL-2), monocyte chemotactic protein 2 (MCP-2), interferon gamma inducible protein-10 (IP-10), interferon gamma (IFN-γ), tumor necrosis factor superfamily member 14 (TNFSF14, also known as LIGHT), monokine induced by gamma interferon (MIG), and granzyme B (P <0.00001). In addition, antigen stimulation increased the expression of heparin-binding EGF-like growth factor (HB-EGF) and activin AB in LTBI samples. In nil tubes, LIGHT was the most significant marker (P <0.0001) and was elevated in LTBI subjects. Other prominent markers in nonstimulated QFT-GIT supernatants were the complement-3 components C3b, iC3b, and C3d, which were upregulated in LTBI and markedly decreased upon stimulation. We found known and novel proteins that warrant further studies for developing improved tests for LTBI, for predicting progression to active disease, and for discriminating LTBI from active TB.
用于诊断潜伏性结核感染（LTBI）的检测方法存在局限性，其在识别进展为活动性结核病（TB）风险最高人群方面的预测价值较低，并且在不同人群中具有不同的敏感性和特异性。确定一种更可靠的LTBI标志物对于结核病的预防和消除至关重要。我们对来自美国移民的样本进行了一项试点研究，这些样本通过三种商业批准的检测方法进行LTBI筛查，即结核菌素皮肤试验（TST）、全血γ干扰素释放试验（QFT-GIT）和结核感染T细胞检测（T-SPOT.TB）。通过高度多重的SOMAscan蛋白质组学分析，对13例结果一致为阳性和26例结果一致为阴性的QFT-GIT上清液进行了分析。刺激上清液中能够区分LTBI与对照的蛋白质包括白细胞介素-2（IL-2）、单核细胞趋化蛋白2（MCP-2）、γ干扰素诱导蛋白10（IP-10）、γ干扰素（IFN-γ）、肿瘤坏死因子超家族成员14（TNFSF14，也称为LIGHT）、γ干扰素诱导单核因子（MIG）和颗粒酶B（P<0.00001）。此外，抗原刺激增加了LTBI样本中肝素结合表皮生长因子（HB-EGF）和激活素AB的表达。在空管中，LIGHT是最显著的标志物（P<0.0001），且在LTBI受试者中升高。未刺激的QFT-GIT上清液中的其他突出标志物是补体3成分C3b、iC3b和C3d，它们在LTBI中上调，并在刺激后显著降低。我们发现了已知和新的蛋白质，这些蛋白质值得进一步研究，以开发改进的LTBI检测方法、预测进展为活动性疾病以及区分LTBI与活动性结核病。
