表达PD-L1的CD14^(++)CD16^(+)单核细胞与ARDS的因果关系:一项孟德尔随机化研究  

Causal relationship between CD14^(++)CD16^(+) monocytes expressing PD-L1 and acute respiratory distress syndrome:a Mendelian randomization study

作　　者：王雅博 崔旭东 杨敬平[2] Wang Yabo;Cui Xudong;Yang Jingping(The Third Clinical Medical College,Inner Mongolia Medical University,Hohhot O10000,China;Department of Respiratory and Critical Care Medicine,the Third Affiliated Hospital of Inner Mongolia Medical University,Baotou 014000,China)

机构地区：[1]内蒙古医科大学第三临床医学院,呼和浩特010000 [2]内蒙古医科大学第三附属医院呼吸与危重症医学科,包头014000

出　　处：《国际呼吸杂志》2024年第11期1298-1305,共8页International Journal of Respiration

基　　金：内蒙古自治区自然科学基金(2023QN08063);中国金属学会冶金安全与健康分会健康卫生科研项目(jkws202313)。

摘　　要：目的采用孟德尔随机化(MR)分析探究表达程序性死亡受体配体1(PD-L1)的CD14^(++)CD16^(+)单核细胞与急性呼吸窘迫综合征(ARDS)之间的因果关系。方法以表达PD-L1的CD14^(++)CD16^(+)单核细胞为暴露因素,以ARDS为结局因素。通过全基因组关联分析数据库获取单核苷酸多态性(SNP)作为工具变量。表达PD-L1的CD14^(++)CD16^(+)单核细胞数据来源于IEU数据库,包含3618例样本;ARDS的汇总数据来源于FinnGen数据库,包含328例样本。采用逆方差加权法(IVW)、MR-Egger回归分析、加权中位数法(WME)进行MR分析,以OR值和95%CI评估表达PD-L1的CD14^(++)CD16^(+)单核细胞与ARDS之间的因果关系。通过MR-Egger截距法、Cochran′sQ检验、留一法进行敏感性分析,检验IVW结果的有效性和稳健性。结果最终纳入16个与暴露因素密切相关的SNP作为工具变量。IVW结果显示表达PD-L1的CD14^(++)CD16^(+)单核细胞数量增加会升高ARDS的发病风险(β=0.178,SE=0.079,OR=1.195,95%CI:1.025~1.394,P=0.023)。MR-Egger回归分析结果与IVW结果一致(β=0.236,SE=0.102,OR=1.266,95%CI:1.036~1.548,P=0.037)。WME结果显示表达PD-L1的CD14^(++)CD16^(+)单核细胞数量与ARDS之间的关联无统计学意义(β=0.163,SE=0.114,OR=1.178,95%CI:0.942~1.473,P=0.152)。IVW(P=0.685)和MR-Egger回归(P=0.674)的Cochran′sQ检验结果均显示不存在异质性。MR-Egger截距法结果表明SNP不存在水平多效性(截距项为-0.034,P=0.395)。留一法敏感性分析结果显示,在逐步剔除各SNP并重复MR分析时,没有观察到对总体结果产生实质性影响,表明结果稳健可信。结论利用MR分析方法推断表达PD-L1的CD14^(++)CD16^(+)单核细胞与ARDS之间可能存在正向因果关系。Objective:To explore the causal relationship between CD14^(++)CD16^(+) monocytes expressing programmed death-ligand 1(PD-L1)and acute respiratory distress syndrome(ARDS)using the Mendelian randomization(MR)analysis.Methods:CD14^(++)CD16^(+) monocytes expressing PD-L1 were used as the exposure factor,and ARDS was used as the outcome factor.Single nucleotide polymorphisms(SNPs)were obtained as instrumental variables through a genome-wide association study database.CD14^(++)CD16^(+) monocytes expressing PD-L1 were obtained from the IEU database,including 3618 samples.The pooled data for ARDS were derived from the FinnGen database and included 328 individuals.The inverse-variance weighted(IVW),MR-Egger regression analysis,and weighted median(WME)were used to evaluate the causal relationship between CD14^(++)CD16^(+) monocytes expressing PD-L1 and ARDS with the estimations of OR and 95%CI.The validity and robustness of IVW results were tested by MR-Egger intercept method,Cochran′s Q test,and retention one method.Results:Finally,16 SNPs closely related to exposure factors were included as instrumental variables.IVW results showed that the increase in the number of CD14^(++)CD16^(+) monocytes expressing PD-L1 increased the risk of ARDS(β=0.178,SE=0.079,OR=1.195,95%CI:1.025-1.394,P=0.023).The results of MR-Egger regression analysis were consistent with those of IVW findings(β=0.236,SE=0.102,OR=1.266,95%CI:1.036-1.548,P=0.037).WME results showed no significant association between the number of CD14^(++)CD16^(+) monocytes expressing PD-L1 and ARDS(β=0.163,SE=0.114,OR=1.178,95%CI:0.942-1.473,P=0.152).There was no heterogeneity in the Cochran′s Q test for IVW(P=0.685)and MR-Egger regression(P=0.674).The MR-Egger intercept method showed no horizontal pleiotropy in SNPs(the intercep t=-0.034,P=0.395).The results of the retention one method sensitivity analysis showed no substantial effect on the overall results when each SNP was gradually excluded and the MR analysis was repeated,indicating that the results were robust

关 键 词：呼吸窘迫综合征 孟德尔随机化分析 单核细胞 程序性死亡受体配体1 

分 类 号：R563.8[医药卫生—呼吸系统]