Qi Xiangjia, Gao Liqian, Qi Lifeng
Department of Neurology, Liaocheng People's Hospital, Liaocheng, China.
Brain Behav. 2025 Feb;15(2):e70298. doi: 10.1002/brb3.70298.
This study aims to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and Guillain-Barré syndrome (GBS) using a two-sample Mendelian randomization (MR) approach.
Publicly available summary data from genome-wide association studies (GWAS) were utilized for comprehensive analysis. A genome-wide and human leukocyte antigen association study conducted by Guillaume Butler-Laporte et al. (n = 9724) examined 46 types of antibody-mediated immune responses. GWAS summary statistics for GBS were obtained from the FinnGen consortium (n = 215,931) comprising European populations. The primary method for MR analysis was the inverse-variance weighted (IVW) method. Various sensitivity analyses were conducted to assess the heterogeneity and pleiotropy of the findings.
The IVW method indicates a negative correlation between elevated levels of Epstein-Barr virus (EBV) viral capsid antigen (VCA) p18 antibody and the risk of GBS (OR = 0.79, 95% confidence interval [CI]: 0.65-1.85, p = 0.012). Elevated levels of Toxoplasma gondii surface antigen 1 (sag1) antibody also show a negative correlation with the risk of GBS (OR = 0.79, 95% CI: 0.67-0.92, p = 0.003). No evidence of heterogeneity or horizontal pleiotropy was found in the MR analysis.
Elevated levels of EBV VCA p18 and T. gondii sag1 antibodies appear to be negatively correlated with the risk of GBS, suggesting that immune responses to these pathogens may play a protective role. However, the CI for the EBV VCA p18 association includes 1, indicating the need for caution in interpreting this result. Further research, including mechanistic studies and broader immune profiling, is needed to confirm these findings and explore the underlying pathways.
本研究旨在采用两样本孟德尔随机化（MR）方法，调查针对感染因子的抗体介导免疫反应与吉兰 - 巴雷综合征（GBS）之间的潜在因果关系。
利用公开可用的全基因组关联研究（GWAS）汇总数据进行综合分析。纪尧姆·巴特勒 - 拉波特等人进行的一项全基因组和人类白细胞抗原关联研究（n = 9724）检测了46种抗体介导的免疫反应。GBS的GWAS汇总统计数据来自包含欧洲人群的芬兰基因组联盟（n = 215,931）。MR分析的主要方法是逆方差加权（IVW）法。进行了各种敏感性分析，以评估研究结果的异质性和多效性。
IVW法表明，爱泼斯坦 - 巴尔病毒（EBV）病毒衣壳抗原（VCA）p18抗体水平升高与GBS风险呈负相关（优势比[OR] = 0.79，95%置信区间[CI]：0.65 - 1.85，p = 0.012）。弓形虫表面抗原1（sag1）抗体水平升高也与GBS风险呈负相关（OR = 0.79，95% CI：0.67 - 0.92，p = 0.003）。在MR分析中未发现异质性或水平多效性的证据。
EBV VCA p18和弓形虫sag1抗体水平升高似乎与GBS风险呈负相关，这表明对这些病原体的免疫反应可能起保护作用。然而，EBV VCA p18关联的CI包含1，这表明在解释这一结果时需要谨慎。需要进一步的研究，包括机制研究和更广泛的免疫谱分析，以证实这些发现并探索潜在途径。
