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

Hanyu Zhou,1 Qiaolin Liu,1 Duanbo Lv,1 Yinghao Zheng,1 Zhenlong Xing2 1Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Joint Orthopedics, Guangdong Provincial Hospital of Integrated Traditional and Western Medicine, Foshan, Guangdong, People’s Republic of ChinaCorrespondence: Zhenlong Xing, Department of Joint Orthopedics, Guangdong Provincial Hospital of Integrated Traditional and Western Medicine, No. 16, South Fifth Road, Guicheng Street, Foshan, Guangdong, People’s Republic of China, Tel +86 15015578028, Email [email protected]: 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.Keywords: antibody-mediated immune responses, rheumatoid arthritis, Gout, Mendelian randomization