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通过双向双样本孟德尔随机化研究探索抗体介导的免疫反应与痛风和类风湿关节炎的相互作用机制。

Exploring the Interaction Mechanisms of Antibody-Mediated Immune Responses with Gout and Rheumatoid Arthritis Through a Bidirectional Two-Sample Mendelian Randomization Study.

作者信息

Zhou Hanyu, Liu Qiaolin, Lv Duanbo, Zheng Yinghao, Xing Zhenlong

机构信息

Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.

Department of Joint Orthopedics, Guangdong Provincial Hospital of Integrated Traditional and Western Medicine, Foshan, Guangdong, People's Republic of China.

出版信息

J Pain Res. 2025 May 27;18:2707-2738. doi: 10.2147/JPR.S508813. eCollection 2025.

DOI:10.2147/JPR.S508813
PMID:40458379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12127211/
Abstract

PURPOSE

Gout and Rheumatoid arthritis (RA) are two prevalent non-infectious inflammatory joint diseases that can occur independently or concurrently. The effects and mechanisms related to antibody-mediated immune responses and both Gout and RA remain unclear. The research seeks to investigate the potential causal association and offer a novel perspective for their prevention and treatment strategies.

METHODS

The study employed the bidirectional two-sample Mendelian randomization (MR) analysis for investigation. Datasets comprising 46 antibody-mediated immune responses, as well as those for Gout and RA, were curated from published genome-wide association studies (GWAS). For the causality analysis, methods such as Inverse Variance Weighted (IVW), Weighted Median, Simple Mode, MR-Egger, and Weighted Mode were utilized. We chose MR pleiotropy residual sum and outlier (MR-PRESSO), IVW, MR-Egger, and Leave-one-out for sensitivity analysis to enhance the reliability of the results.

RESULTS

We meticulously excluded the results that exhibited pleiotropy and instability. Finally, four antibody-mediated immune responses have been found as causal factors in the development of Gout: Anti-chlamydia trachomatis IgG seropositivity, Anti-human herpes virus 6 IE1B IgG seropositivity, Helicobacter pylori GroEL antibody levels, and Polyomavirus 2 JC VP1 antibody levels; Two antibody-mediated immune responses influence RA causally: BK polyomavirus VP1 antibody levels, and Helicobacter pylori Catalase antibody levels. In the reverse analysis, three antibody-mediated immune responses could be influenced by Gout: BK polyomavirus VP1 antibody levels, Chlamydia trachomatis tarp-D F2 antibody levels, and Varicella zoster virus glycoproteins E and I antibody levels; Two antibody-mediated immune responses could be causally affected by RA: Anti-human herpes virus 7 IgG seropositivity, and Merkel cell polyomavirus VP1 antibody levels.

CONCLUSION

The research indicated that antibody-mediated immune responses establish a causal link with this two non-infectious inflammatory joint diseases: Gout and RA, offering new avenues and perspectives for the future prophylaxis and treatment of diseases from an immunological standpoint.

摘要

目的

痛风和类风湿关节炎（RA）是两种常见的非感染性炎性关节疾病，可单独或同时发生。与抗体介导的免疫反应以及痛风和RA相关的影响和机制仍不清楚。本研究旨在调查潜在的因果关联，并为其预防和治疗策略提供新的视角。

方法

本研究采用双向两样本孟德尔随机化（MR）分析进行调查。从已发表的全基因组关联研究（GWAS）中整理出包含46种抗体介导的免疫反应以及痛风和RA的数据集。在因果关系分析中，使用了逆方差加权（IVW）、加权中位数、简单模式、MR-Egger和加权模式等方法。我们选择MR多效性残差和异常值（MR-PRESSO）、IVW、MR-Egger和留一法进行敏感性分析，以提高结果的可靠性。

结果

我们精心排除了表现出多效性和不稳定性的结果。最终，发现四种抗体介导的免疫反应是痛风发生的因果因素：抗沙眼衣原体IgG血清阳性、抗人疱疹病毒6 IE1B IgG血清阳性、幽门螺杆菌GroEL抗体水平和多瘤病毒2 JC VP1抗体水平；两种抗体介导的免疫反应对RA有因果影响：BK多瘤病毒VP1抗体水平和幽门螺杆菌过氧化氢酶抗体水平。在反向分析中，三种抗体介导的免疫反应可能受痛风影响：BK多瘤病毒VP1抗体水平、沙眼衣原体tarp-D F2抗体水平和水痘带状疱疹病毒糖蛋白E和I抗体水平；两种抗体介导的免疫反应可能受RA因果影响：抗人疱疹病毒7 IgG血清阳性和默克尔细胞多瘤病毒VP1抗体水平。

结论

该研究表明，抗体介导的免疫反应与这两种非感染性炎性关节疾病——痛风和RA建立了因果联系，从免疫学角度为未来疾病的预防和治疗提供了新的途径和视角。

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