Zeng Xiangrui, Song Rui, Zhang Zheng, Yao Jinni, Liao Heqiang, Wang Congyu, Xu Zhe, Yang Huaicheng
Graduate School of Bengbu Medical University, Bengbu, China.
Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Anhui University of Science and Technology, Huainan, China.
Medicine (Baltimore). 2025 Sep 19;104(38):e44248. doi: 10.1097/MD.0000000000044248.
Over the past 2 decades, the prevalence of cholecystitis has increased significantly, a trend believed to be influenced by improvements in quality of life and changes in lifestyle habits. However, the precise etiology of cholecystitis remains unclear. Although gallstones are commonly associated with this condition, recent studies suggest that immune cells also play a critical role in their development. This study investigated the relationship between cholecystitis and CD45 on CD33br HLA-DR+ immune cells, focusing on the mediating role of glycine levels, using Mendelian randomization (MR). The primary analytical approach employed was inverse variance weighting (IVW) complemented by additional methods, such as MR-Egger, weighted median, simple mode, and weighted mode. Horizontal pleiotropy and heterogeneity were evaluated to ensure the robustness of the MR findings, and a "leave-one-out" analysis was conducted to explore potential mediating effects. IVW analysis revealed that the association between cholecystitis and CD45 on CD33br HLA-DR+ immune cells yielded an odds ratio of 1.039 (95% confidence interval: 1.012-1.067, P = .004). Mediation analysis further indicated that glycine levels mediated this relationship, with a significant mediating effect of 6.87% (P = .0046). Notably, cholecystitis did not exhibit a reverse causal effect of CD45 on CD33br HLA-DR+ levels (P = .545; IVW odds ratio = 1.044, 95% confidence interval: 0.907-1.201). These findings suggested that the association between CD45 on CD33br HLA-DR+ immune cells and cholecystitis is mediated by glycine levels. This study provides novel insights into cholecystitis pathogenesis, highlighting the potential role of metabolic factors in immune-mediated inflammation. These results offer a new perspective on the underlying mechanisms of cholecystitis and suggest potential metabolic intervention targets for its prevention.
在过去20年中，胆囊炎的患病率显著上升，这一趋势被认为受到生活质量改善和生活习惯变化的影响。然而，胆囊炎的确切病因仍不清楚。虽然胆结石通常与这种疾病相关，但最近的研究表明，免疫细胞在其发展中也起着关键作用。本研究使用孟德尔随机化（MR）方法，调查了胆囊炎与CD33br HLA-DR+免疫细胞上CD45之间的关系，重点关注甘氨酸水平的中介作用。采用的主要分析方法是逆方差加权（IVW），并辅以其他方法，如MR-Egger、加权中位数、简单模式和加权模式。评估了水平多效性和异质性，以确保MR结果的稳健性，并进行了“留一法”分析，以探索潜在的中介效应。IVW分析显示，胆囊炎与CD33br HLA-DR+免疫细胞上CD45之间的关联产生的优势比为1.039（95%置信区间：1.012-1.067，P = 0.004）。中介分析进一步表明，甘氨酸水平介导了这种关系，显著中介效应为6.87%（P = 0.0046）。值得注意的是，胆囊炎并未表现出CD45对CD33br HLA-DR+水平的反向因果效应（P = 0.545；IVW优势比 = 1.044，95%置信区间：0.907-1.201）。这些发现表明，CD33br HLA-DR+免疫细胞上的CD45与胆囊炎之间的关联是由甘氨酸水平介导的。本研究为胆囊炎发病机制提供了新的见解，突出了代谢因素在免疫介导炎症中的潜在作用。这些结果为胆囊炎的潜在机制提供了新的视角，并为其预防提出了潜在的代谢干预靶点。
