The Third School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Graduate School of Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Endocrinol (Lausanne). 2024 Sep 3;15:1438097. doi: 10.3389/fendo.2024.1438097. eCollection 2024.
Increasing evidence indicates a close relationship between alterations in human immune cells and plasma metabolites with Rheumatoid Arthritis (RA). However, limited studies have left the causal relationships behind these links unclear.
A bidirectional Mendelian Randomization (MR) study was conducted, combined with mediation analysis, using data from genome-wide association study database covering 731 immune cell phenotypes and 1,400 plasma metabolite traits to explore their causal relationships with RA and potential mediating effects. The primary method used for MR analysis was inverse-variance weighted and False Discovery Rate (FDR) correction was applied to verify the robustness of our results.
HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194-1.694; P < 0.001; P = 0.012) increased the risk of developing RA. CD19 on IgD+ CD38- naive (B cell group) (OR, 0.969; 95% CI, 0.954-0.985; P < 0.001; P = 0.021) reduced the risk of developing RA. RA was a risk factor for HLA DR on CD14- CD16+ monocytes (monocyte group) (OR, 1.242; 95% CI, 1.102-1.401; P < 0.001; P = 0.047). RA was a protective factor for memory B cell %lymphocyte (B cell group) (OR, 0.861; 95% CI, 0.795-0.933; P < 0.001; P = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711-0.904; P < 0.001; P = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726-0.913; P < 0.001; P = 0.046), CD24 on IgD+ CD24+ B cells (B cell group) (OR, 0.857; 95% CI, 0.793-0.927; P < 0.001; P = 0.038), and CD24 on unswitched memory B cells (B cell group) (OR, 0.867; 95% CI, 0.797-0.942; P < 0.001; P = 0.050). Increasing levels of docosatrienoate (22:3n3) (OR, 0.886; 95% CI, 0.838-0.936; P < 0.001; P = 0.023) significantly reduced the risk of developing RA. The mediating effect of plasma metabolites in this context was not established.
This study provides genetic evidence for the intricate relationships between immune cells, plasma metabolites, and RA, highlighting the potential mechanisms involved. This will contribute to future directions in precision medicine and research.
越来越多的证据表明，人类免疫细胞和血浆代谢物的改变与类风湿关节炎（RA）之间存在密切关系。然而，有限的研究使得这些关联背后的因果关系仍不清楚。
采用双向孟德尔随机化（MR）研究，结合中介分析，利用涵盖 731 种免疫细胞表型和 1400 种血浆代谢物特征的全基因组关联研究数据库，探讨它们与 RA 的因果关系及其潜在的中介效应。MR 分析的主要方法是逆方差加权，应用假发现率（FDR）校正来验证我们结果的稳健性。
CD33-HLA DR+（髓样细胞群）上的 HLA DR（OR，1.422；95%CI，1.194-1.694；P<0.001；P=0.012）增加了患 RA 的风险。IgD+CD38-幼稚（B 细胞群）上的 CD19（OR，0.969；95%CI，0.954-0.985；P<0.001；P=0.021）降低了患 RA 的风险。RA 是 CD14-CD16+单核细胞（单核细胞群）上 HLA DR（OR，1.242；95%CI，1.102-1.401；P<0.001；P=0.047）的风险因素。RA 是记忆 B 细胞%淋巴细胞（B 细胞群）（OR，0.861；95%CI，0.795-0.933；P<0.001；P=0.050）、CD4+CD8dim T 细胞%淋巴细胞（TBNK 群）（OR，0.802；95%CI，0.711-0.904；P<0.001；P=0.043）、CD4+CD8dim T 细胞%白细胞（TBNK 群）（OR，0.814；95%CI，0.726-0.913；P<0.001；P=0.046）、CD24 上的 IgD+CD24+B 细胞（B 细胞群）（OR，0.857；95%CI，0.793-0.927；P<0.001；P=0.038）和无转换记忆 B 细胞上的 CD24（B 细胞群）（OR，0.867；95%CI，0.797-0.942；P<0.001；P=0.050）的保护因素。二十二碳三烯酸（22:3n3）（OR，0.886；95%CI，0.838-0.936；P<0.001；P=0.023）水平的升高显著降低了患 RA 的风险。在这种情况下，血浆代谢物的中介效应尚未建立。
本研究为免疫细胞、血浆代谢物与 RA 之间的复杂关系提供了遗传证据，强调了其中涉及的潜在机制。这将有助于未来精准医学和研究的方向。
