School of Public Health and Management, Youjiang Medical University for Nationalities, Baise, China.
Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Key Discipline Platform of Tuberculosis Control, Guangxi Centre for Disease Control and Prevention, Nanning, China.
Front Immunol. 2024 May 21;15:1398403. doi: 10.3389/fimmu.2024.1398403. eCollection 2024.
Despite extensive research on the relationship between pulmonary tuberculosis (PTB) and inflammatory factors, more robust causal evidence has yet to emerge. Therefore, this study aims to screen for inflammatory proteins that may contribute to the susceptibility to PTB in different populations and to explain the diversity of inflammatory and immune mechanisms of PTB in different ethnicity.
The inverse variance weighted (IVW) model of a two-sample Mendelian Randomization (MR) study was employed to conduct causal analysis on data from a genome-wide association study (GWAS). This cohort consisting PTB GWAS datasets from two European and two East Asian populations, as well as 91 human inflammatory proteins collected from 14,824 participants. Colocalization analysis aimed to determine whether the input inflammatory protein and PTB shared the same causal single nucleotide polymorphisms (SNPs) variation within the fixed region, thereby enhancing the robustness of the MR Analysis. Meta-analyses were utilized to evaluate the combined causal effects among different datasets.
In this study, we observed a significant negative correlation between tumor necrosis factor-beta levels (The alternative we employ is Lymphotoxin-alpha, commonly referred to as LT) ( < 0.05) and tumor necrosis factor receptor superfamily member 9 levels (TNFRSF9) ( < 0.05). These two inflammatory proteins were crucial protective factors against PTB. Additionally, there was a significant positive correlation found between interleukin-20 receptor subunit alpha levels (IL20Ra) ( < 0.05), which may elevate the risk of PTB. Colocalization analysis revealed that there was no overlap in the causal variation between LT and PTB SNPs. A meta-analysis further confirmed the significant combined effect of LT, TNFRSF9, and IL20Ra in East Asian populations ( < 0.05).
Levels of specific inflammatory proteins may play a crucial role in triggering an immune response to PTB. Altered levels of LT and TNFRSF9 have the potential to serve as predictive markers for PTB development, necessitating further clinical validation in real-world settings to ascertain the impact of these inflammatory proteins on PTB.
尽管已经对肺结核（PTB）与炎症因子之间的关系进行了广泛的研究，但仍然缺乏强有力的因果证据。因此，本研究旨在筛选可能导致不同人群易患 PTB 的炎症蛋白，并解释不同种族人群中 PTB 的炎症和免疫机制的多样性。
采用两样本孟德尔随机化（MR）研究的逆方差加权（IVW）模型，对来自两个欧洲和两个东亚人群的 PTB 全基因组关联研究（GWAS）数据集以及来自 14824 名参与者的 91 个人类炎症蛋白进行因果分析。共定位分析旨在确定输入炎症蛋白和 PTB 是否在固定区域内共享相同的因果单核苷酸多态性（SNP）变异，从而增强 MR 分析的稳健性。采用荟萃分析评估不同数据集之间的综合因果效应。
在本研究中，我们观察到肿瘤坏死因子-β水平（我们采用的替代物是淋巴毒素-α，通常称为 LT）（<0.05）和肿瘤坏死因子受体超家族成员 9 水平（TNFRSF9）（<0.05）之间存在显著负相关。这两种炎症蛋白是 PTB 的重要保护因素。此外，白细胞介素-20 受体亚单位α水平（IL20Ra）（<0.05）与 PTB 之间存在显著正相关，这可能会增加 PTB 的风险。共定位分析表明，LT 和 PTB SNP 之间的因果变异没有重叠。荟萃分析进一步证实了 LT、TNFRSF9 和 IL20Ra 在东亚人群中的显著综合效应（<0.05）。
特定炎症蛋白的水平可能在引发对 PTB 的免疫反应中发挥关键作用。LT 和 TNFRSF9 水平的改变可能成为 PTB 发展的预测标志物，需要在真实环境中进一步进行临床验证，以确定这些炎症蛋白对 PTB 的影响。
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