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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1438097

Effect of the Immune Cells and Plasma Metabolites on Rheumatoid Arthritis: A Mediated Mendelian Randomization Study

Provisionally accepted
Qi-Pei Liu Qi-Pei Liu 1Hong-Cheng Du Hong-Cheng Du 2*Ping-Jin Xie Ping-Jin Xie 3*Sheng-Ting Chai Sheng-Ting Chai 4*
  • 1 The Third School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 2 Graduate School, Guangxi University of Chinese Medicine, Guangxi, China
  • 3 Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, China
  • 4 The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

The final, formatted version of the article will be published soon.

    Background: 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. Methods: 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. Results: HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194–1.694; P < 0.001; PFDR = 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; PFDR = 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; PFDR  = 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; PFDR = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711–0.904; P < 0.001; PFDR  = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726–0.913; P < 0.001; PFDR  = 0.046), CD24 on IgD+ CD24+ B cells (B cell group) (OR, 0.857; 95% CI, 0.793–0.927; P < 0.001; PFDR  = 0.038), and CD24 on unswitched memory B cells (B cell group) (OR, 0.867; 95% CI, 0.797–0.942; P < 0.001; PFDR  = 0.050). Increasing levels of docosatrienoate (22:3n3) (OR, 0.886; 95% CI, 0.838–0.936; P < 0.001; PFDR = 0.023) significantly reduced the risk of developing RA. The mediating effect of plasma metabolites in this context was not established. Conclusion: 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.

    Keywords: immune cells, Plasma metabolites, Rheumatoid arthritis, bidirectional causality, Mediation analysis, causality

    Received: 19 Jun 2024; Accepted: 15 Aug 2024.

    Copyright: © 2024 Liu, Du, Xie and Chai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hong-Cheng Du, Graduate School, Guangxi University of Chinese Medicine, Guangxi, 530001, China
    Ping-Jin Xie, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, China
    Sheng-Ting Chai, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

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