Yu Yiyang, Liu Guangxu, Zhang Rui, Chen Baojiang, Luan Zhongqiu
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Renshou County Chinese Medicine Hospital, Meishan, Sichuan, China.
Medicine (Baltimore). 2025 Jun 6;104(23):e42774. doi: 10.1097/MD.0000000000042774.
Prior studies have explored the contribution of immune cells in membranous nephropathy (MN). This study utilized Mendelian randomization (MR) to further explore 731 immune cell subtypes on MN, offering robust evidence for their causality. Genetic information for 731 subtypes of immune cells and MN was obtained from genome-wide association studies. Inverse variance weighting (IVW) was employed as the primary analytical method. To reinforce the findings, additional methods, MR-Egger, weighted median, and weighted mode, were employed, along with sensitivity analyses to ensure robustness and stability. Using the IVW method, MR analysis identified significant positive correlations between 17 immune cell subtypes and MN (P < .05, OR > 1) and negative correlations for 29 subtypes (P < .05, OR < 1). In the reverse MR analysis, MN exhibited positive associations with 2 subtypes (P < .05, OR > 1) and negatively correlated with another 4 subtypes (P < .05, OR < 1). None of these associations showed signs of horizontal pleiotropy (P > .05). This extensive bidirectional two-sample MR analysis provides insights into the complex causal links between certain immune subtypes and MN, underscoring the sophisticated interactions between components of the immune system and MN.
先前的研究探讨了免疫细胞在膜性肾病（MN）中的作用。本研究利用孟德尔随机化（MR）进一步探究了731种免疫细胞亚型与MN的关系，为它们之间的因果关系提供了有力证据。免疫细胞和MN的731种亚型的遗传信息来自全基因组关联研究。采用逆方差加权（IVW）作为主要分析方法。为了加强研究结果，还采用了其他方法，如MR-Egger、加权中位数和加权模式，并进行了敏感性分析以确保稳健性和稳定性。使用IVW方法，MR分析确定了17种免疫细胞亚型与MN之间存在显著正相关（P < 0.05，OR > 1），29种亚型存在负相关（P < 0.05，OR < 1）。在反向MR分析中，MN与2种亚型呈正相关（P < 0.05，OR > 1），与另外4种亚型呈负相关（P < 0.05，OR < 1）。这些关联均未显示出水平多效性的迹象（P > 0.05）。这种广泛的双向双样本MR分析揭示了某些免疫亚型与MN之间复杂的因果联系，强调了免疫系统各组成部分与MN之间复杂的相互作用。
