Antibody Responses to EBV and Toxoplasma and Their Genetic Links to Guillain-Barré Syndrome: A Mendelian Randomization Study.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.