PDF(Pubmed)
Abstract：
Prior research has identified associations between immune cells and aplastic anaemia (AA); however, the causal relationships between them have not been conclusively established. A two-sample Mendelian randomisation analysis was conducted to investigate the causal link between 731 immune cell signatures and AA risk using publicly available genetic data. Four types of immune signatures, including relative cell, absolute cell (AC), median fluorescence intensities and morphological parameters, were considered sensitivity analyses were also performed to verify the robustness of the results and assess potential issues such as heterogeneity and horizontal pleiotropy. Following multiple test adjustments using the False Discovery Rate (FDR) method, no statistically significant impact of any immunophenotype on AA was observed. However, twelve immunophenotypes exhibited a significant correlation with AA without FDR correction (p of IVW < 0.01), of which eight were harmful to AA: CD127- CD8br %T cell (Treg panel), CD25 on IgD + CD38dim (B cell panel), CD38 on naive-mature B cell (B cell panel), CD39 + resting Treg % CD4 Treg (Treg panel), CD39 + secreting Treg AC (Treg panel), CD8 on CD28 + CD45RA- CD8br (Treg panel), HLA DR + NK AC (TBNK panel), Naive DN (CD4-CD8-) AC (Maturation stages of T cell panel); and four were protective to AA: CD86 on CD62L + myeloid DC (cDC panel), DC AC (cDC panel), DN (CD4-CD8-) NKT %T cell (TBNK panel), and TD CD4 + AC (Maturation stages of T cell panel). The results of this study demonstrate a close link between immune cells and AA by genetic means, thereby improving the current understanding of the interaction between immune cells and AA risk and providing guidance for future clinical research.
摘要：
先前的研究已经确定了免疫细胞和再生障碍性贫血（AA）之间的关联;然而，它们之间的因果关系尚未确定无疑。使用公开的遗传数据，进行了双样本孟德尔随机化分析，以研究731个免疫细胞特征与AA风险之间的因果关系。四种类型的免疫特征，包括相对细胞，绝对细胞(AC)，中值荧光强度和形态参数，还进行了敏感性分析，以验证结果的稳健性，并评估异质性和水平多效性等潜在问题。使用错误发现率(FDR)方法进行多次测试调整后，未观察到任何免疫表型对AA的统计学显著影响.然而,12种免疫表型与未经FDR校正的AA呈显著相关性(IVWp<0.01),其中8个对AA有害：CD127-CD8br%T细胞（Treg面板），IgD+CD38dim（B细胞面板）上的CD25，幼稚成熟B细胞（B细胞组）上的CD38，CD39+静息Treg%CD4Treg（Treg面板），CD39+分泌TregAC（Treg面板），CD28+CD45RA-CD8br上的CD8（Treg面板），HLADR+NKAC（TBNK面板），幼稚DN（CD4-CD8-）AC（T细胞组的成熟期）;和四个保护AA：CD62L骨髓DC上的CD86（cDC组），DCAC(cDC面板),DN（CD4-CD8-）NKT%T细胞（TBNK面板），和TDCD4+AC(T细胞组的成熟期)。这项研究的结果表明，通过遗传手段，免疫细胞与AA之间存在着密切的联系，从而提高目前对免疫细胞与AA风险相互作用的认识,为今后的临床研究提供指导。
