[免疫细胞与败血症之间的因果关系:基于孟德尔随机法的研究]。

Q3 Medicine
Qiushuang Yu, Lingxu Li, Yina Tao, Longqiang Zhang, Junfeng Hu, Huaxue Wang
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引用次数: 0

摘要

目的利用孟德尔随机化(MR)方法研究免疫细胞与不同类型败血症之间的因果关系,并找出与败血症有因果关系的免疫细胞表型:各种循环免疫细胞表型的汇总数据来自 GWAS 目录(GCST90001391-GCST90002121)。败血症数据来自英国生物库数据库。单核苷酸多态性(SNP)被用作工具变量。用 P < 5×10-6 的相关性阈值来识别强相关的工具变量,并用代码剔除联系不平衡和 F 值 < 10 的工具变量。以反向方差加权法(IVW)为主要研究方法,评价结果的稳定性和可靠性,包括 Cochran's Q 检验、MR-Egger 回归和留一法。根据剔除横向褶积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。用比值比(OR)和95%置信区间(95%CI)表示结果的效应值:结果:CD14上的CD16-CD16+;单核细胞在脓毒症中具有水平多向性(OR=0.965 4,95%CI为0.933 5-0.998 3,P=0.039 6)。有五种免疫表型与败血症相关类型存在反向因果关系。在排除了具有水平褶积性和反向因果关系的免疫细胞表型后,共有42种免疫细胞表型与败血症有关,36种免疫细胞表型与败血症(重症监护中28天死亡)有关,32种免疫细胞表型与败血症(重症监护)有关,44种免疫细胞表型与败血症(28天死亡)有关,30种免疫细胞表型与败血症(75岁以下)有潜在的因果关系。经错误发现率(FDR)校正后,IgD- CD38br上的BAFF-R与脓毒症(28天死亡)呈负强相关(OR=0.737 8,95%CI为0.635 9-0.856 0,P=6.05×10-5,PFDR=0.044 2):多种免疫细胞表型可能对脓毒症有保护作用,尤其是IgD- CD38br表达的BAFF-R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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Causal association between immune cells and sepsis: a based on Mendelian randomization method study].

Objective: 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.

Methods: 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 < 5×10-6 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.

Results: CD16 on CD14-CD16+; 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 = 6.05×10-5, PFDR = 0.044 2).

Conclusions: 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.

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来源期刊
Zhonghua wei zhong bing ji jiu yi xue
Zhonghua wei zhong bing ji jiu yi xue Medicine-Critical Care and Intensive Care Medicine
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