Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Vaccines and Immunity Theme, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, Gambia.
Front Immunol. 2020 Sep 9;11:572620. doi: 10.3389/fimmu.2020.572620. eCollection 2020.
Blood-based biomarkers have been proposed as an alternative to current sputum-based treatment monitoring methods in active tuberculosis (ATB). The aim of this study was to validate previously described phenotypic, activation, and cytokine markers of treatment response in a West African cohort.
Whole blood immune responses to ESAT-6/CFP-10 (EC) and purified protein derivative (PPD) were measured in twenty adults at baseline and after 2 months of standard TB treatment. Patients were classified as fast or slow responders based on a negative or positive sputum culture result at 2 months, respectively. Cellular expression of activation markers (CD38, HLA-DR), memory markers (CD27), and functional intracellular cytokine and proliferation (IFN-γ, Ki-67, TNF-α) markers were measured using multi-color flow cytometry.
There was a significant increase in the proportion of CD4CD27 cells expressing CD38 and HLA-DR following EC stimulation at 2 months compared to baseline ( = 0.0328 and = 0.0400, respectively). Following PPD stimulation, slow treatment responders had a significantly higher proportion of CD8CD27IFN-γ ( = 0.0105) and CD4CD27HLA-DRCD38 ( = 0.0077) T cells than fast responders at baseline. Receiver operating curve analysis of these subsets resulted in 80% sensitivity and 70 and 100% specificity, respectively (AUC of 0.82, = 0.0156 and 0.84, = 0.0102).
Our pilot data show reductions in expression of T cell activation markers were seen with treatment, but this was not associated with fast or slow sputum conversion at 2 months. However, baseline proportions of activated T cell subsets are potentially predictive of the subsequent speed of response to treatment.
已有研究提出，在活动性肺结核（ATB）中，血液生物标志物可以替代目前基于痰的治疗监测方法。本研究旨在验证之前在西非队列中描述的治疗反应的表型、激活和细胞因子标志物。
在 20 名成年人中，在基线和标准 TB 治疗 2 个月后，分别测量全血对 ESAT-6/CFP-10（EC）和纯化蛋白衍生物（PPD）的免疫反应。根据 2 个月时痰培养结果的阴性或阳性，将患者分别归类为快速或慢速反应者。使用多色流式细胞术测量细胞表面活化标志物（CD38、HLA-DR）、记忆标志物（CD27）和功能性细胞内细胞因子和增殖（IFN-γ、Ki-67、TNF-α）标志物的表达。
与基线相比，在 2 个月时 EC 刺激后 CD4CD27 细胞表达 CD38 和 HLA-DR 的比例显著增加（=0.0328 和=0.0400）。在 PPD 刺激下，与快速反应者相比，慢速反应者在基线时 CD8CD27IFN-γ（=0.0105）和 CD4CD27HLA-DRCD38（=0.0077）T 细胞的比例明显更高。对这些亚群的接收者操作特征曲线分析得出，敏感性分别为 80%和 70%和 100%，特异性分别为 70%和 100%（AUC 为 0.82，=0.0156 和 0.84，=0.0102）。
我们的初步数据显示，治疗后 T 细胞活化标志物的表达减少，但这与 2 个月时的痰快速或慢速转化无关。然而，基线时激活的 T 细胞亚群的比例可能预测随后对治疗的反应速度。
