目的:采用两样本孟德尔随机化(MR)方法研究731种免疫细胞表型与散发型克雅氏病(sporadic Creutzfeld-Jacob disease, sCJD)发病风险的因果效应。方法:在全基因组关联研究数据库(genome wide association study, GWAS)中筛选符合条件的73...目的:采用两样本孟德尔随机化(MR)方法研究731种免疫细胞表型与散发型克雅氏病(sporadic Creutzfeld-Jacob disease, sCJD)发病风险的因果效应。方法:在全基因组关联研究数据库(genome wide association study, GWAS)中筛选符合条件的731种免疫细胞表型及散发型克雅氏病的因果关系。共纳入了四种类型的免疫特征(MFI, RC, AC和MP)。综合敏感性分析用于验证结果的异质性和水平多向性。结果:IVW结果显示免疫细胞与免疫细胞发病风险存在因果效应,其中四种免疫表型对散发型克雅氏病的保护作用:CD24+ CD27+ %lymphocyte (OR = 0.925, 95% CI: 0.863~0.991, P = 0.027)、CX3CR1 on monocyte (OR = 0.924, 95% CI: 0.859~0.994, P = 0.034)、SSC-A on myeloid DC (OR = 0.857, 95% CI: 0.740~0.993, P = 0.040)、Unsw mem AC (OR = 0.844, 95% CI: 0.718~0.992, P = 0.040)。六种免疫表型对散发型克雅氏病的危害作用:CD28− CD8dim %T cell (OR = 1.099, 95% CI: 1.012~1.195, P = 0.025)、CD40 on CD14− CD16+ monocyte (OR = 1.062, 95% CI: 1.000~1.129, P = 0.050)、CD62L− myeloid DC %DC (OR = 1.092, 95% CI: 1.009~1.183, P = 0.013)、Mo MDSC AC (OR = 1.123, 95% CI: 1.036~1.217, P = 0.005)、SSC-A on CD4+ (OR = 1.147, 95% CI: 1.035~1.271, P = 0.028)、SSC-A on NK (OR = 1.116, 95% CI: 1.010~1.232, P = 0.031)。结论:我们的研究通过基因手段证明了免疫细胞与散发型克雅氏病之间的密切联系,从而为今后的临床研究与预防提供了指导。Objective: This paper aims to investigate the causal effects of 731 immune cell phenotypes and the risk of sporadic Creutzfeld-Jacob disease (sCJD) using a two-sample Mendelian randomization (MR) approach. Methods: Eligible 731 immune cell phenotypes were screened for causal association with sporadic Creutzfeldt-Jakob disease (sCJD) in the genome wide association study (GWAS) database. A total of four types of immune profiles (MFI, RC, AC and MP) were included. Integrated sensitivity analysis was used to validate the heterogeneity and horizontal multidirectionality of the results. Results: IVW results showed a causal effect of immune cells and risk of immune cell pathogenesis, with four immune phenotypes protective against disseminated Creutzfeldt-Jakob disease: CD24+ CD27+ %lymphocyte (OR = 0.925, 95% CI: 0.863~0.991, P = 0.027), CX3CR1 on monocyte (OR = 0.924, 95% CI: 0.859~0.994, P = 0.034), SSC-A on myeloid DC (OR = 0.857, 95% CI: 0.740~0.993, P = 0.040), Unsw mem AC (OR = 0.844, 95% CI: 0.718~0.992, P = 0.040). The hazardous effects of six immunophenotypes on disseminated Creutzfeldt-Jakob disease: CD28− CD8dim %T cell (OR = 1.099, 95% CI: 1.012~1.195, P = 0.025), CD40 on CD14− CD16+ monocyte (OR = 1.062, 95% CI: 1.000~1.129, P = 0.050), CD62L− myeloid DC %DC (OR = 1.092, 95% CI: 1.009~1.183, P = 0.013), Mo MDSC AC (OR = 1.123, 95% CI: 1.036~1.217, P = 0.005), SSC-A on CD4+ (OR = 1.147, 95% CI: 1.035~1.271, P = 0.028), SSC-A on NK (OR = 1.116, 95% CI: 1.010~1.232, P = 0.031). Conclusion: Our study demonstrated a close association between immune cells and disseminated Creutzfeldt-Jakob disease by genetic means, thus providing guidance for future clinical research and prevention.展开更多
文摘目的:采用两样本孟德尔随机化(MR)方法研究731种免疫细胞表型与散发型克雅氏病(sporadic Creutzfeld-Jacob disease, sCJD)发病风险的因果效应。方法:在全基因组关联研究数据库(genome wide association study, GWAS)中筛选符合条件的731种免疫细胞表型及散发型克雅氏病的因果关系。共纳入了四种类型的免疫特征(MFI, RC, AC和MP)。综合敏感性分析用于验证结果的异质性和水平多向性。结果:IVW结果显示免疫细胞与免疫细胞发病风险存在因果效应,其中四种免疫表型对散发型克雅氏病的保护作用:CD24+ CD27+ %lymphocyte (OR = 0.925, 95% CI: 0.863~0.991, P = 0.027)、CX3CR1 on monocyte (OR = 0.924, 95% CI: 0.859~0.994, P = 0.034)、SSC-A on myeloid DC (OR = 0.857, 95% CI: 0.740~0.993, P = 0.040)、Unsw mem AC (OR = 0.844, 95% CI: 0.718~0.992, P = 0.040)。六种免疫表型对散发型克雅氏病的危害作用:CD28− CD8dim %T cell (OR = 1.099, 95% CI: 1.012~1.195, P = 0.025)、CD40 on CD14− CD16+ monocyte (OR = 1.062, 95% CI: 1.000~1.129, P = 0.050)、CD62L− myeloid DC %DC (OR = 1.092, 95% CI: 1.009~1.183, P = 0.013)、Mo MDSC AC (OR = 1.123, 95% CI: 1.036~1.217, P = 0.005)、SSC-A on CD4+ (OR = 1.147, 95% CI: 1.035~1.271, P = 0.028)、SSC-A on NK (OR = 1.116, 95% CI: 1.010~1.232, P = 0.031)。结论:我们的研究通过基因手段证明了免疫细胞与散发型克雅氏病之间的密切联系,从而为今后的临床研究与预防提供了指导。Objective: This paper aims to investigate the causal effects of 731 immune cell phenotypes and the risk of sporadic Creutzfeld-Jacob disease (sCJD) using a two-sample Mendelian randomization (MR) approach. Methods: Eligible 731 immune cell phenotypes were screened for causal association with sporadic Creutzfeldt-Jakob disease (sCJD) in the genome wide association study (GWAS) database. A total of four types of immune profiles (MFI, RC, AC and MP) were included. Integrated sensitivity analysis was used to validate the heterogeneity and horizontal multidirectionality of the results. Results: IVW results showed a causal effect of immune cells and risk of immune cell pathogenesis, with four immune phenotypes protective against disseminated Creutzfeldt-Jakob disease: CD24+ CD27+ %lymphocyte (OR = 0.925, 95% CI: 0.863~0.991, P = 0.027), CX3CR1 on monocyte (OR = 0.924, 95% CI: 0.859~0.994, P = 0.034), SSC-A on myeloid DC (OR = 0.857, 95% CI: 0.740~0.993, P = 0.040), Unsw mem AC (OR = 0.844, 95% CI: 0.718~0.992, P = 0.040). The hazardous effects of six immunophenotypes on disseminated Creutzfeldt-Jakob disease: CD28− CD8dim %T cell (OR = 1.099, 95% CI: 1.012~1.195, P = 0.025), CD40 on CD14− CD16+ monocyte (OR = 1.062, 95% CI: 1.000~1.129, P = 0.050), CD62L− myeloid DC %DC (OR = 1.092, 95% CI: 1.009~1.183, P = 0.013), Mo MDSC AC (OR = 1.123, 95% CI: 1.036~1.217, P = 0.005), SSC-A on CD4+ (OR = 1.147, 95% CI: 1.035~1.271, P = 0.028), SSC-A on NK (OR = 1.116, 95% CI: 1.010~1.232, P = 0.031). Conclusion: Our study demonstrated a close association between immune cells and disseminated Creutzfeldt-Jakob disease by genetic means, thus providing guidance for future clinical research and prevention.
文摘为了探究马立克氏病(MD)易感鸡和抗性鸡脾脏组织转录组的特征差异,试验选择200只7日龄、健康的霞烟鸡(MD抗性品系核心群的后代),每只试验鸡腹腔注射含2500 pfu血清Ⅰ型马立克氏病病毒(MDV-1)超强毒株GX0101的血毒,攻毒210 d后,选取感染MDV-1超强毒株GX0101且脾脏明显具有MD肿瘤的鸡只作为易感组,未感染MDV-1超强毒株GX0101且无任何MD临床症状的鸡只作为MD抗性组,处死后提取脾脏组织总RNA,采用转录组测序技术进行差异表达基因(DEGs)的筛选,并进行基因本体(gene ontology,GO)功能富集分析、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路分析和原发性免疫缺陷通路相关基因的表达分析。结果表明:在MD易感组与MD抗性组脾脏组织中共筛选得到152个DEGs,相对于MD易感组,MD抗性组脾脏组织有92个DEGs显著下调,60个DEGs显著上调(|lbFold Change|>1,FDR<0.05);共发现48个显著富集(P<0.05)GO条目,其中生物学过程共富集到23个条目,细胞组分共富集到16个条目,分子功能共富集到9个条目;筛选得到的DEGs在细胞周期、嘧啶代谢和原发性免疫缺陷通路等13个信号通路中显著富集。在原发性免疫缺陷通路中,与MD易感组比较,MD抗性组脾脏组织TNFRSF13B基因[编码钙调节因子(TACI)]显著下调(P<0.05),CD8α基因显著上调(P<0.05)。说明MD抗性鸡可通过下调体液免疫缺陷相关基因TACI和上调细胞免疫缺陷相关基因CD8α来提高机体对MD的抗性。
