Background While T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studied, the role of B-cells and antibodies are less well characterised. The aim of this study was to assess levels of Mtb-specific IgG + plasmablasts across the Mtb infection spectrum. Methods Patients with active TB were analysed at baseline and 6 months of therapy (n = 20).Their exposed household contacts (HHC) included individuals with latent TB infection (LTBI; n = 20); evident at baseline; individuals with a negative Tuberculin Skin Test (TST) at baseline who became; positive at 6 months (converters; n = 11) and those who remained negative (non-converters; n = 10). An e x-vivo B-cell ELISPOT was performed to analyse plasmablast responses. Results Frequencies of ESAT-6/CFP-10 (EC)- but not Whole Cell Lysate (WCL)-specific plasmablasts were significantly higher in patients with active TB pre-treatment compared to post-treatment (p = 0.002) and compared to HHC with LTBI (p < 0.0001). Conversely, total IgG + plasmablasts were significantly decreased in TB patients at baseline. No difference was seen in levels of plasmablasts between TST converters and non-converters at baseline. Conclusions We show that EC-specific plasmablast levels are differentially modulated during TB infection and disease, with levels highest during active TB. These data provide new insights into TB biomarker development and avenues for novel immune interventions.

中文翻译：

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结核分枝杆菌特异性浆母细胞水平在结核感染和疾病中受到不同调节

背景 虽然 T 细胞对结核分枝杆菌 (Mtb) 的反应已得到广泛研究，但 B 细胞和抗体的作用还没有得到很好的表征。本研究的目的是评估 Mtb 感染谱中 Mtb 特异性 IgG + 浆母细胞的水平。方法 在基线和治疗 6 个月时对活动性结核病患者进行分析（n = 20）。他们的家庭接触者（HHC）包括潜伏性结核病感染者（LTBI；n = 20）；基线明显；在基线时结核菌素皮肤试验 (TST) 呈阴性的个体成为；6 个月时呈阳性（转化者；n = 11）和那些保持阴性（非转化者；n = 10）。进行体外 B 细胞 ELISPOT 以分析浆母细胞反应。结果 与治疗后 (p = 0.002) 和 HHC 相比，活动性结核病患者治疗前 ESAT-6/CFP-10 (EC) 而非全细胞裂解物 (WCL) 特异性浆母细胞的频率显着更高LTBI (p < 0.0001)。相反，在基线时，TB 患者的总 IgG + 浆母细胞显着减少。在基线时，TST 转化者和非转化者之间的浆母细胞水平没有差异。结论 我们显示 EC 特异性浆母细胞水平在 TB 感染和疾病期间受到不同程度的调节，在活动性 TB 期间水平最高。这些数据为结核病生物标志物的开发和新型免疫干预措施提供了新的见解。在基线时，TB 患者的总 IgG + 浆母细胞显着减少。在基线时，TST 转化者和非转化者之间的浆母细胞水平没有差异。结论 我们显示 EC 特异性浆母细胞水平在 TB 感染和疾病期间受到不同程度的调节，在活动性 TB 期间水平最高。这些数据为结核病生物标志物的开发和新型免疫干预措施提供了新的见解。在基线时，TB 患者的总 IgG + 浆母细胞显着减少。在基线时，TST 转化者和非转化者之间的浆母细胞水平没有差异。结论 我们表明，在 TB 感染和疾病期间，EC 特异性浆母细胞水平受到不同程度的调节，在活动性 TB 期间水平最高。这些数据为结核病生物标志物的开发和新型免疫干预措施提供了新的见解。