Khalid Hamza, Pierneef Louise, van Hooij Anouk, Zhou Zijie, de Jong Danielle, Tjon Kon Fat Elisa, Connelley Timothy K, Hope Jayne C, Corstjens Paul L A M, Geluk Annemieke
Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
Division of Immunology, The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Front Vet Sci. 2023 Aug 15;10:1193332. doi: 10.3389/fvets.2023.1193332. eCollection 2023.
Bovine tuberculosis (bTB), caused by () infection in cattle, is an economically devastating chronic disease for livestock worldwide. Efficient disease control measures rely on early and accurate diagnosis using the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), followed by culling of positive animals. Compromised performance of TST and IGRA, due to BCG vaccination or co-infections with non-tuberculous mycobacteria (NTM), urges improved diagnostics. Lateral flow assays (LFAs) utilizing luminescent upconverting reporter particles (UCP) for quantitative measurement of host biomarkers present an accurate but less equipment- and labor-demanding diagnostic test platform. UCP-LFAs have proven applications for human infectious diseases. Here, we report the development of UCP-LFAs for the detection of six bovine proteins (IFN-γ, IL-2, IL-6, CCL4, CXCL9, and CXCL10), which have been described by ELISA as potential biomarkers to discriminate infected from naïve and BCG-vaccinated cattle. We show that, in line with the ELISA data, the combined PPDb-induced levels of IFN-γ, IL-2, IL-6, CCL4, and CXCL9 determined by UCP-LFAs can discriminate challenged animals from naïve (AUC range: 0.87-1.00) and BCG-vaccinated animals (AUC range: 0.97-1.00) in this cohort. These initial findings can be used to develop a robust and user-friendly multi-biomarker test (MBT) for bTB diagnosis.
牛结核病（bTB）由牛感染（）引起，是一种对全球家畜具有经济破坏性的慢性疾病。有效的疾病控制措施依赖于使用结核菌素皮肤试验（TST）和干扰素-γ释放测定（IGRA）进行早期准确诊断，随后扑杀阳性动物。由于卡介苗接种或与非结核分枝杆菌（NTM）共同感染，TST和IGRA的性能受到影响，这促使人们改进诊断方法。利用发光上转换报告颗粒（UCP）对宿主生物标志物进行定量测量的侧向流动分析（LFA）提供了一个准确但对设备和劳动力要求较低的诊断测试平台。UCP-LFA已被证明可用于人类传染病的诊断。在此，我们报告了用于检测六种牛蛋白（IFN-γ、IL-2、IL-6、CCL4、CXCL9和CXCL1）的UCP-LFA的开发，ELISA已将这些蛋白描述为区分感染牛与未感染牛和卡介苗接种牛的潜在生物标志物。我们表明，与ELISA数据一致，通过UCP-LFA测定的PPDb诱导的IFN-γ、IL-2、IL-6、CCL4和CXCL9的联合水平可以区分该队列中受攻击的动物与未感染动物（AUC范围：0.87-1.00）和卡介苗接种动物（AUC范围：0.97-1.00）。这些初步发现可用于开发一种用于牛结核病诊断的强大且用户友好的多生物标志物测试（MBT）。
