Yu Qiushuang, Li Lingxu, Tao Yina, Zhang Longqiang, Hu Junfeng, Wang Huaxue
Department of Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui, China.
Department of Respiratory Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui, China. Corresponding author: Wang Huaxue, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024 Aug;36(8):821-828. doi: 10.3760/cma.j.cn121430-20240527-00462.
To investigate the causal association between immune cell and different types of sepsis by using Mendelian randomization (MR) method, and to find the immune cell phenotypes causally associated with sepsis.
Summary data for various circulating immune cell phenotypes were obtained from the GWAS catalog (GCST90001391-GCST90002121). Sepsis data were sourced from the UK Biobank database. Single nucleotide polymorphisms (SNP) were used as instrumental variables. The correlation threshold of P < 5×10 was used to identify the strongly correlated instrumental variables, and the code was used to remove the linkage disequilibrium and the instrumental variables with F-value < 10. Inverse variance weighting (IVW) was used as the main research method to evaluate the stability and reliability of the results, including Cochran's Q test, MR-Egger regression and Leave one out. Reverse MR analysis was performed based on the immunophenotypic results of the removal of horizontal pleiotropy, and the immune cell phenotype with one-way causal association was obtained. Odds ratio (OR) and 95% confidence interval (95%CI) were used to represent the effect value of the results.
CD16 on CD14CD16; monocyte had horizontal pleiotropy in sepsis (OR = 0.965 4, 95%CI was 0.933 5-0.998 3, P = 0.039 6). There were five immunophenotypes that had reverse causal associations with the types associated with sepsis. After excluding immune cell phenotypes with horizontal pleiotropy and reverse causation, a total of 42 immune cell phenotypes with sepsis, 36 immune cell phenotypes with sepsis (28-day death in critical care), 32 immune cell phenotypes with sepsis (critical care), 44 immune cell phenotypes with sepsis (28-day death), and 30 immune cell phenotypes had potential causal associations with sepsis (under 75 years old). After false discovery rate (FDR) correction, the correlations between BAFF-R on IgD CD38br and sepsis (28-day death) were negative and strong (OR = 0.737 8, 95%CI was 0.635 9-0.856 0, P = 6.05×10, P = 0.044 2).
A variety of immune cell phenotypes may have a protective effect on sepsis, especially BAFF-R on IgD CD38br expression is negatively correlated with sepsis (28-day death), which provides a new idea for immune modulation therapy in sepsis.
采用孟德尔随机化（MR）方法研究免疫细胞与不同类型脓毒症之间的因果关联，并找出与脓毒症存在因果关联的免疫细胞表型。
从全基因组关联研究目录（GCST90001391 - GCST90002121）获取各种循环免疫细胞表型的汇总数据。脓毒症数据来自英国生物银行数据库。单核苷酸多态性（SNP）用作工具变量。使用P < 5×10的相关阈值来识别强相关的工具变量，并使用代码去除连锁不平衡和F值< 10的工具变量。采用逆方差加权（IVW）作为主要研究方法来评估结果的稳定性和可靠性，包括 Cochr an's Q检验、MR - Egger回归和留一法。基于去除水平多效性的免疫表型结果进行反向MR分析，得到具有单向因果关联的免疫细胞表型。比值比（OR）和95%置信区间（95%CI）用于表示结果的效应值。
CD14CD16;单核细胞上的CD16在脓毒症中存在水平多效性（OR = 0.965 4，95%CI为0.933 5 - 0.998 3，P = 0.039 6）。有五种免疫表型与脓毒症相关类型存在反向因果关联。在排除具有水平多效性和反向因果关系的免疫细胞表型后，共有42种免疫细胞表型与脓毒症、36种免疫细胞表型与脓毒症（重症监护中28天死亡）、32种免疫细胞表型与脓毒症（重症监护）、44种免疫细胞表型与脓毒症（28天死亡）以及30种免疫细胞表型与脓毒症（75岁以下）存在潜在因果关联。经过错误发现率（FDR）校正后，IgD CD38br上的BAFF - R与脓毒症（28天死亡）之间的相关性为负且较强（OR = 0.737 8，95%CI为0.635 9 - 0.856 0，P = 6.05×10，P = 0.044 2）。
多种免疫细胞表型可能对脓毒症具有保护作用，尤其是IgD CD38br上的BAFF - R表达与脓毒症（28天死亡）呈负相关，这为脓毒症的免疫调节治疗提供了新思路。
