Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Nat Med. 2011 Mar;17(3):372-6. doi: 10.1038/nm.2299. Epub 2011 Feb 20.
Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4+ T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4+ T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4+ T cells is a new tool for the rapid diagnosis of active tuberculosis disease.
快速诊断活动性结核分枝杆菌（Mtb）感染仍然是临床和实验室面临的挑战。我们通过多色流式细胞术分析了 Mtb 特异性 T 细胞的细胞因子谱（干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白细胞介素-2（IL-2））。我们研究了潜伏性 Mtb 感染和活动性结核病患者中 Mtb 特异性 CD4+T 细胞反应。结果表明，在活动性疾病患者中，单阳性 TNF-α Mtb 特异性 CD4+T 细胞的比例显著增加，该参数是诊断活动性疾病与潜伏性感染的最强预测指标。我们在一个由 101 名结核病诊断未知的患者组成的队列中验证了该参数的使用。基于流式细胞术的检测的灵敏度和特异性分别为 67%和 92%，阳性预测值为 80%，阴性预测值为 92.4%。因此，单阳性 TNF-α Mtb 特异性 CD4+T 细胞的比例是快速诊断活动性结核病的新工具。
