■观察性研究表明,原发性硬化性胆管炎(PSC)的免疫失调主要涉及肠道来源的免疫细胞。然而,外周血免疫细胞与PSC之间的因果关系仍未得到充分理解.
■进行了双向双样本孟德尔随机化(MR)分析,以确定PBC和731免疫细胞之间的因果效应。所有数据集均从公开可用的遗传数据库中提取。选择标准方差逆加权(IVW)方法作为因果关系分析的主要方法。进行Cochran的Q统计和MR-Egger截距以评估异质性和多效性。
■在正向MR分析中,CD62L+髓样DC(OR=1.136,95%CI=1.032-1.250,p=0.009)和CD62L-髓样DCAC(OR=1.267,95%CI=1.086-1.477,p=0.003)上CD11c的表达率与较高的PSC风险相关。CD28对静息调节性T细胞(Treg)(OR=0.724,95%CI=0.630-0.833,p<0.001)和CD3对分泌Treg(OR=0.893,95%CI=0.823-0.969,p=0.007)的增加与PSC的风险呈负相关。在反向MR分析中,PSC被鉴定为对EMCD8+T细胞AC具有遗传因果效应,CD8+T细胞AC,CD28-CD127-CD25++CD8+T细胞AC,CD28-CD25++CD8+T细胞AC,CD28-CD8+T细胞/CD8+T细胞,CD28-CD8+T细胞AC,和CD45RA-CD28-CD8+T细胞AC。
■我们的研究表明了PSC和免疫细胞之间因果关系的证据,这可能为将来PSC的诊断和治疗提供潜在的基础。
UNASSIGNED: Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood.
UNASSIGNED: A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran\'s Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy.
UNASSIGNED: In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032-1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086-1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630-0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823-0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28- CD127- CD25++ CD8+ T cell AC, CD28- CD25++ CD8+ T cell AC, CD28- CD8+ T cell/CD8+ T cell, CD28- CD8+ T cell AC, and CD45 RA- CD28- CD8+ T cell AC.
UNASSIGNED: Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.