Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2024 Jul 15;15:1417716. doi: 10.3389/fimmu.2024.1417716. eCollection 2024.
Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.
Genetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.
Our MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.
Our MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.
败血症是一种危及生命的器官功能障碍，是由宿主对感染的失调反应引起的，但免疫表型与败血症之间的潜在因果关系仍不清楚。
与免疫表型相关的遗传变异作为孟德尔随机化（MR）中的工具变量（IVs），以阐明免疫表型对三种败血症结局的因果影响。此外，还进行了两步 MR 分析，以确定免疫表型与三种败血症结局之间的显著潜在中介。
我们的 MR 分析表明，免疫表型与败血症结局之间存在显著关联，免疫表型与败血症易感性、严重程度和死亡率分别相关的变异体分别为 36、36 和 45。具体而言，我们的分析强调了 CD14+CD16+单核细胞表型是所有三种败血症结局的一个重要因素，其比值比（OR）和相应的置信区间（CI）表明其对败血症（OR=1.047，CI：1.001-1.096）、重症监护病房中的败血症（OR=1.139，CI：1.014-1.279）和败血症相关的 28 天死亡率（OR=1.218，CI：1.104-1.334）的影响。中介分析确定了 7 种细胞因子作为 91 种潜在细胞因子中的显著中介，包括白细胞介素-5（IL-5）、S100A12、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、T 细胞表面糖蛋白 CD6 同工型、半胱氨酸蛋白酶抑制剂 D、白细胞介素-18（IL-18）和尿激酶型纤溶酶原激活物（uPA）。此外，反向 MR 分析显示败血症结局对免疫表型没有因果影响。
我们的 MR 研究表明，免疫表型与败血症患者的易感性、严重程度和死亡率显著相关，首次提供了免疫特征与其潜在风险之间存在显著关联的有力证据。这些信息对于临床医生和患者做出明智的决策非常宝贵，值得进一步关注。
