■脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍,然而,免疫表型与脓毒症之间的潜在因果关系尚不清楚.
■与免疫表型相关的遗传变异在孟德尔随机化(MR)中用作工具变量(IVs),以阐明免疫表型对三种脓毒症结局的因果影响。此外,我们进行了两步MR分析,以确定免疫表型与3个脓毒症结局之间的显著潜在介质.
■我们的MR分析表明免疫表型与败血症结局之间存在显着关联,36、36和45与易感性相关的免疫表型,严重程度,和败血症的死亡率,分别。具体来说,我们的分析强调了CD14+CD16+单核细胞表型是所有三个脓毒症结局的重要因素,比值比(OR)和相应的置信区间(CI)表明其对脓毒症的影响(OR=1.047,CI:1.001-1.096),重症监护病房脓毒症(OR=1.139,CI:1.014-1.279),与脓毒症相关的28天死亡率(OR=1.218,CI:1.104-1.334)。中介分析确定了七种细胞因子是91种潜在细胞因子中的重要介质,包括白细胞介素-5(IL-5),S100A12,TNF相关凋亡诱导配体(TRAIL),T细胞表面糖蛋白CD6亚型,胱抑素D,白细胞介素-18(IL-18),尿激酶型纤溶酶原激活物(uPA)。此外,反向MR分析显示,脓毒症结局对免疫表型无因果关系.
■我们的MR研究表明免疫表型与易感性显著相关,严重程度,和败血症患者的死亡率,提供,第一次,免疫性状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定是非常宝贵的,值得进一步关注。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.