Max Planck Institute for Infection Biology, Berlin, Germany.
Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
Clin Infect Dis. 2020 Jun 24;71(1):30-40. doi: 10.1093/cid/ciz785.
Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. In this study, we aimed to identify correlates of protection against Mtb infection.
Two groups of Mtb-exposed contacts of tuberculosis (TB) patients were recruited and classified according to their Mtb infection status using the tuberculin skin test (TST; cohort 1) or QuantiFERON (QFT; cohort 2). A negative reading at baseline with a positive reading at follow-up classified TST or QFT converters and a negative reading at both time points classified TST or QFT nonconverters. Ribonucleic acid sequencing, Mtb proteome arrays, and metabolic profiling were performed.
Several genes were found to be differentially expressed at baseline between converters and nonconverters. Gene set enrichment analysis revealed a distinct B-cell gene signature in TST nonconverters compared to converters. When infection status was defined by QFT, enrichment of type I interferon was observed. A remarkable area under the curve (AUC) of 1.0 was observed for IgA reactivity to Rv0134 and an AUC of 0.98 for IgA reactivity to both Rv0629c and Rv2188c. IgG reactivity to Rv3223c resulted in an AUC of 0.96 and was markedly higher compared to TST nonconverters. We also identified several differences in metabolite profiles, including changes in biomarkers of inflammation, fatty acid metabolism, and bile acids. Pantothenate (vitamin B5) was significantly increased in TST nonconverters compared to converters at baseline (q = 0.0060).
These data provide new insights into the early protective response to Mtb infection and possible avenues to interfere with Mtb infection, including vitamin B5 supplementation.Analysis of blood from highly exposed household contacts from The Gambia who never develop latent Mycobacterium tuberculosis infection shows distinct transcriptomic, antibody, and metabolomic profiles compared to those who develop latent tuberculosis infection but prior to any signs of infection.
迫切需要预防结核分枝杆菌（Mtb）感染的策略。在这项研究中，我们旨在确定对 Mtb 感染的保护相关因素。
招募了两组 Mtb 暴露的结核患者接触者，并根据结核菌素皮肤试验（TST；队列 1）或 QuantiFERON（QFT；队列 2）的感染状态进行分类。基线时为阴性读数，随访时为阳性读数，将 TST 或 QFT 转化者分类，两次读数均为阴性读数，将 TST 或 QFT 非转化者分类。进行了核糖核酸测序、Mtb 蛋白质组阵列和代谢物分析。
在基线时，发现了几个在转化者和非转化者之间表达差异的基因。基因集富集分析显示，TST 非转化者与转化者相比存在明显的 B 细胞基因特征。当以 QFT 定义感染状态时，观察到 I 型干扰素的富集。Rv0134 的 IgA 反应的曲线下面积（AUC）为 1.0，Rv0629c 和 Rv2188c 的 IgA 反应的 AUC 为 0.98。Rv3223c 的 IgG 反应的 AUC 为 0.96，明显高于 TST 非转化者。我们还发现了代谢物谱的几个差异，包括炎症标志物、脂肪酸代谢和胆汁酸的变化。与转化者相比，TST 非转化者在基线时 pantothenate（维生素 B5）显著增加（q = 0.0060）。
这些数据为 Mtb 感染的早期保护反应提供了新的见解，并为干预 Mtb 感染提供了可能的途径，包括维生素 B5 补充。对来自冈比亚的高度暴露的家庭接触者的血液进行分析，这些接触者从未发展为潜伏性结核分枝杆菌感染，与发展为潜伏性结核病感染但尚未出现任何感染迹象的接触者相比，具有明显的转录组、抗体和代谢组学特征。
