Immune cells mediate the effect of plasma lipidomes on IgA nephropathy: a Mendelian randomization study.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY
Renal Failure Pub Date : 2025-12-01 Epub Date: 2025-05-06 DOI:10.1080/0886022X.2025.2498631
Quanxin Li, Ye Chen, Yahan Zhu, Xiaoyang Cui, Jichen Pan, Xiao Li, Xiaolin Liu
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引用次数: 0

Abstract

Background: IgA nephropathy (IgAN) is a leading cause of chronic kidney disease, often associated with dyslipidemia and immune dysfunction. This study employs Mendelian randomization (MR) to investigate the causal relationship between plasma lipidomes and IgAN, with a focus on the potential mediating role of immune cells.

Methods: We analyzed the 179 genetically predicted plasma lipidomes and the IgAN gene using two-sample Mendelian randomization (TSMR) and multivariable MR based on summary-level data from a genome-wide association study, and the results were validated by liquid chromatography-mass spectrometry. Furthermore, we quantified the proportional effect of immune cell-mediated lipidomes on IgAN using TSMR.

Results: This study identified significant causal relationships of 3 lipidomes on IgAN risk by examining 179 lipidome traits as exposures. To investigate whether the impact of the 3 lipid groups on IgAN is specific, we performed TSMR analyses using 3 lipidomes as exposure factors and 4 nephritides as outcomes. Specifically, only phosphatidylinositol (18:1_20:4) was found to have a significant negative relationship with IgAN incidence (IVW method, p = 0.01, OR = 0.71, 95% CI = 0.55 - 0.92). Our further analysis focused on 8 immune cells associated with IgAN. We identified 2 immune cell phenotypes that may contribute to phosphatidylinositol (18:1_20:4)-mediated IgAN by careful screening.

Conclusions: Our findings provide robust genetic evidence supporting a causal link between plasma lipidomes and IgAN, with immune cells acting as potential mediators. Phosphatidylinositol (18:1_20:4) emerges as a promising biomarker for IgAN risk stratification, early detection, and therapeutic intervention. Modulating its plasma levels may offer novel avenues for IgAN management.

免疫细胞介导血浆脂质体对IgA肾病的影响:一项孟德尔随机研究。
背景:IgA肾病(IgAN)是慢性肾脏疾病的主要原因,通常与血脂异常和免疫功能障碍有关。本研究采用孟德尔随机化(Mendelian randomization, MR)研究血浆脂质体与IgAN之间的因果关系,重点关注免疫细胞的潜在介导作用。方法:基于一项全基因组关联研究的汇总数据,采用双样本孟德尔随机化(TSMR)和多变量磁共振(MR)分析了179个基因预测的血浆脂质组和IgAN基因,并通过液相色谱-质谱法验证了结果。此外,我们使用TSMR量化了免疫细胞介导的脂质体对IgAN的比例效应。结果:本研究通过检测179种脂质组特征,确定了3种脂质组与IgAN风险的显著因果关系。为了研究3种脂质组对IgAN的影响是否具有特异性,我们使用3种脂质组作为暴露因素,4种肾肽作为结果进行了TSMR分析。其中,只有磷脂酰肌醇(18:1_20:4)与IgAN发病率呈显著负相关(IVW法,p = 0.01, OR = 0.71, 95% CI = 0.55 ~ 0.92)。我们进一步分析了与IgAN相关的8个免疫细胞。通过仔细筛选,我们确定了两种可能参与磷脂酰肌醇(18:1_20 . 4)介导的IgAN的免疫细胞表型。结论:我们的研究结果提供了强有力的遗传证据,支持血浆脂质体和IgAN之间的因果关系,免疫细胞作为潜在的介质。磷脂酰肌醇(18:1_20:4)作为IgAN风险分层、早期检测和治疗干预的一种有前景的生物标志物。调节其血浆水平可能为IgAN的管理提供新的途径。
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来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
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