用孟德尔随机化方法研究免疫细胞表型与HSP27的因果关系

doi:10.3969/j.issn.1006-6233.2024.08.012

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Abstract 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.

Key words： Immune cells HSP27 Mendelian randomization analysis Causal analysis Sensitivity analysis

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.08.012 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I8/1296

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