Xu Meiling, Su Meihua, Chen Guangyong
Department of Rheumatology and Immunology, China-Japan, Union Hospital of Jilin University Xiantai, Street No.126, Changchun, Jilin Province, 130033, China.
Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun City, China.
Viral Immunol. 2024 Dec;37(10):451-458. doi: 10.1089/vim.2024.0056. Epub 2024 Nov 20.
This study aims to evaluate the estimate of causal relationship between Epstein-Barr virus (EBV) antibody levels and autoimmune diseases (AIDs), such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), through bidirectional two-sample Mendelian randomization (MR) analysis. Despite 50 years of research into the link between EBV infection and AIDs, inconsistent results persist due to the complex mechanisms of EBV within the body. We utilized large-scale genome-wide association studies (GWAS) data from the Integrative Epidemiology Unit (IEU) Open GWAS Project database to conduct rigorous MR analysis, incorporating various sensitivity analyses to assess potential impacts and ensure robustness. EBV antibodies (including VCA-IgG, ZEBRA-IgG, EBNA-1-IgG, and EA-D-IgG) were used as exposure variables, whereas RA and SLE served as outcome variables. In the reverse analysis, RA and SLE were treated as exposure variables and EBV antibodies as outcome variables. When EBV antibodies are designated as the exposure variables, the random-effects inverse-variance weighted (IVW) analysis indicated a significant negative genetic causal relationship between EBV EA-D antibody levels and RA ( = 0.007, odds ratio [OR] = 0.700, 95% confidence interval [CI] = [0.539-0.907]). No significant genetic causal relationship was found between SLE and EBV antibody levels. When RA and SLE are designated as the exposure variables, the random-effects IVW analysis revealed significant positive genetic causal relationships between SLE and EBV ZEBRA antibody levels ( = 0.009, OR = 1.028, 95% CI = [1.007-1.050]) and EBV EA-D antibody levels ( = 0.005, OR = 1.032, 95% CI = [1.009-1.054]). No significant genetic causal relationship was observed between RA and EBV antibody levels. This study offers compelling evidence of a causal relationship between EBV antibody levels and AIDs through MR analysis. Our findings lay a new foundation and perspective for future research directions, clinical prognosis, and treatment.
本研究旨在通过双向双样本孟德尔随机化（MR）分析，评估爱泼斯坦-巴尔病毒（EBV）抗体水平与自身免疫性疾病（AIDs）之间因果关系的估计值，这些疾病包括类风湿关节炎（RA）和系统性红斑狼疮（SLE）。尽管对EBV感染与AIDs之间的联系进行了50年的研究，但由于EBV在体内的复杂机制，结果仍然不一致。我们利用综合流行病学单位（IEU）开放GWAS项目数据库中的大规模全基因组关联研究（GWAS）数据进行严格的MR分析，并纳入各种敏感性分析以评估潜在影响并确保稳健性。EBV抗体（包括VCA-IgG、ZEBRA-IgG、EBNA-1-IgG和EA-D-IgG）用作暴露变量，而RA和SLE用作结果变量。在反向分析中，RA和SLE被视为暴露变量，EBV抗体被视为结果变量。当将EBV抗体指定为暴露变量时，随机效应逆方差加权（IVW）分析表明，EBV EA-D抗体水平与RA之间存在显著的负遗传因果关系（P = 0.007，比值比[OR] = 0.700，95%置信区间[CI] = [0.539 - 0.907]）。未发现SLE与EBV抗体水平之间存在显著的遗传因果关系。当将RA和SLE指定为暴露变量时，随机效应IVW分析显示SLE与EBV ZEBRA抗体水平（P = 0.009，OR = 1.028，95% CI = [1.007 - 1.050]）和EBV EA-D抗体水平（P = 0.005，OR = 1.032，95% CI = [1.009 - 1.054]）之间存在显著的正遗传因果关系。未观察到RA与EBV抗体水平之间存在显著的遗传因果关系。本研究通过MR分析提供了EBV抗体水平与AIDs之间因果关系的有力证据。我们的发现为未来的研究方向、临床预后和治疗奠定了新的基础和视角。
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