The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, China.
Medicine (Baltimore). 2024 Oct 4;103(40):e39871. doi: 10.1097/MD.0000000000039871.
Recent empirical research posits a link between lymphocyte subgroups and both the incidence and prognosis of sepsis. Nevertheless, the potential influence of multiple confounding variables obscures any clear causative correlation. Utilizing a 2-sample Mendelian randomization approach, we conducted a meta-analysis of lymphocyte subgroups. In a genome-wide association study, flow cytometry was applied to a lymphocyte subgroup comprising 3757 Sardinians to identify genes influenced by blood immune cells. The sepsis meta-analysis data were sourced from the UK Biobank database, including 11,643 treatment groups and 47,841 control groups. Inverse variance-weighted, Mendelian randomization-Egger regression, weighted median, simple mode, and weighted mode methods were deployed to ascertain the causative relationship between lymphocyte subgroup and sepsis. Cochran Q test, the Mendelian randomization-Egger intercept test, and funnel plots were leveraged to assess the robustness of study findings. The inverse variance-weighted analysis disclosed that the absolute count of CD4 regulatory T cells (CD4 Treg AC) within the lymphocyte subgroup has a causative link to an elevated risk of sepsis, with an odds ratio of 1.08 and a 95% confidence interval of 1.02 to 1.15 (P = .011). Compared to individuals not subjected to this factor, those exposed to CD4 Treg AC have a marginally elevated sepsis risk by approximately 0.08%. No causative relationships were observed between sepsis risk and the absolute counts of other lymphocyte subgroups such as CD8+ T cells, CD4+ CD8dim T cells, natural killer T cells, B cells (B cell absolute count), and HLA DR+ natural killer cells. The 2-sample Mendelian randomization study indicated a causal relationship between the level of CD4 Treg AC and the increased risk of sepsis. The elevation in circulating lymphocyte subgroups suggests higher susceptibility to sepsis, affirming the immune susceptibility inherent to this condition. The findings from our study may propose potential targets for diagnosis and intervention of sepsis.
最近的实证研究提出，淋巴细胞亚群与败血症的发病率和预后均存在关联。然而，多种混杂因素的潜在影响使得任何明确的因果关系变得模糊不清。我们采用两样本孟德尔随机化方法，对淋巴细胞亚群进行了荟萃分析。在一项全基因组关联研究中，我们对包括 3757 名撒丁岛人在内的淋巴细胞亚群进行了流式细胞术分析，以确定受血液免疫细胞影响的基因。败血症荟萃分析数据来自英国生物银行数据库，包括 11643 个治疗组和 47841 个对照组。我们采用逆方差加权、孟德尔随机化- Egger 回归、加权中位数、简单模式和加权模式方法来确定淋巴细胞亚群与败血症之间的因果关系。我们还利用 Cochran Q 检验、孟德尔随机化- Egger 截距检验和漏斗图来评估研究结果的稳健性。逆方差加权分析表明，淋巴细胞亚群中 CD4 调节性 T 细胞（CD4 Treg AC）的绝对计数与败血症风险升高存在因果关系，比值比为 1.08，95%置信区间为 1.02 至 1.15（P =.011）。与未暴露于这一因素的个体相比，暴露于 CD4 Treg AC 的个体发生败血症的风险略有升高，约为 0.08%。未观察到 CD8+ T 细胞、CD4+ CD8dim T 细胞、自然杀伤 T 细胞、B 细胞（B 细胞绝对计数）和 HLA-DR+自然杀伤细胞等其他淋巴细胞亚群的绝对计数与败血症风险之间存在因果关系。两样本孟德尔随机化研究表明，CD4 Treg AC 水平与败血症风险增加之间存在因果关系。循环淋巴细胞亚群的升高表明对败血症的易感性增加，证实了这种疾病固有的免疫易感性。我们的研究结果可能为败血症的诊断和干预提供潜在的靶点。
