用孟德尔随机化方法研究免疫细胞表型与HSP27的因果关系

Causal Relationship between Immune Cell Phenotypes and HSP27 Using Mendelian Randomization Method

目的:探讨免疫细胞表型对HSP27的因果作用。方法:采用两样本孟德尔随机化(MR)综合分析来确定免疫细胞表型与HSP27表达水平之间的因果关系。基于公开的遗传数据,我们探索了731个免疫细胞表型与HSP27表达的因果关系,总共包括四种类型的免疫特征(中位数荧光强度(MFI)、相对细胞(RC)、绝对细胞(AC)和形态参数(MP))。综合敏感性分析用于验证结果的稳健性、异质性和水平多效性。结果:我们进行了双向FDR校正,HSP27的表达在统计学上对细胞免疫表型没有显著影响(P>0.05)。然而,在研究细胞免疫表型对HSP27的因果影响时,我们发现在三种细胞免疫性状类别(MFI、RC、AC)中,21种免疫表型与HSP27表达存在因果联系(P<0.05)。其中,12种免疫表型可促进HSP27的表达(IVW:P<0.05,OR<1),包括:IgD-CD24-AC;IgD-CD24-%lymphocyte;Myeloid DC AC;CD62L-myeloid DC AC;Activated Treg%CD4 Treg;CD38 on IgD+CD38dim;CCR2 on granulocyte;CD80 on CD62L+myeloid DC;CD80 on monocyte;CD8 on TD CD8br;CD4 on activated&secreting Treg;CD11c on granulocyte。另外9种免疫表型可抑制HSP27的表达(IVW:P<0.05,OR>1),即:CD62L-plas-macytoid DC AC;Naive CD4+AC;CD14+CD16+monocyte AC;CD3 on T cell;CD3 on CD8br;HVEM on CM CD4+;HVEM on naive CD4+;CX3CR1 on CD14-CD16-;CD45 on Mo MDSC。结论:本研究揭示了免疫细胞表型与HSP27之间存在显著的遗传相关性,这对了解HSP27的病理机制具有重要意义。它不仅为未来临床疾病的诊断和治疗提供了新思路,而且有助于开发更准确的生物标志物和治疗方法。此外,我们的研究结果扩展了免疫学的研究成果,并为进一步研究免疫细胞与热休克蛋白在免疫应答和疾病中的相互作用提供了新的证据。

Objective:To investigate the causal effects of immune cell phenotypes on HSP27.Methods:This study utilized a two-sample Mendelian randomization(MR)analysis to determine the causal relationship between immune cell phenotypes and HSP27 expression levels.Based on publicly available genetic data,we explored the causal relationships between 731 immune cell phenotypes and HSP27 expression,encompassing four types of immune traits:median fluorescence intensity(MFI),relative cells(RC),absolute cells(AC),and morphological parameters(MP).Comprehensive sensitivity analyses were used to validate the robustness,heterogeneity,and horizontal pleiotropy of the results.Results:Bidirectional FDR correction showed that HSP27 expression did not significantly affect immune cell phenotypes(P>0.05).However,when examining the causal impact of immune cell phenotypes on HSP27 expression,we found causal relationships in three categories of immune traits(MFI,RC,AC)involving 21 immune phenotypes(P<0.05).Among them,12 immune phenotypes promoted HSP27 expression(IVW:P<0.05,OR<1),including:IgD-CD24-AC;IgD-CD24-%lymphocyte;Myeloid DC AC;CD62L-myeloid DC AC;Activated Treg%CD4 Treg;CD38 on IgD+CD38dim;CCR2 on granulocyte;CD80 on CD62L+myeloid DC;CD80 on monocyte;CD8 on TD CD8br;CD4 on activated&secreting Treg;CD11c on granulocyte.Additionally,9 immune phenotypes inhibited HSP27 expression(IVW:P<0.05,OR>1),namely:CD62L-plasmacytoid DC AC;Naive CD4+AC;CD14+CD16+monocyte AC;CD3 on T cell;CD3 on CD8br;HVEM on CM CD4+;HVEM on naive CD4+;CX3CR1 on CD14-CD16-;CD45 on Mo MDSC.Conclusion:This study reveals a significant genetic correlation between immune cell phenotypes and HSP27,which is important for understanding the pathological mechanisms of HSP27.It provides new insights for the future diagnosis and treatment of clinical diseases and helps develop more accurate biomarkers and therapeutic approaches.Moreover,our findings expand the scope of immunological research and offer new evidence for further studies on the interactions between immune cells and heat shock proteins in immune responses and diseases.