Introduction:
Previous studies suggest an association between herpes virus infections and idiopathic pulmonary fibrosis (IPF), but the causal relationship remains largely unclear. We used bidirectional Mendelian randomization (MR) to investigate the causal effect of crucial antibodies against herpes virus on IPF.

Material and methods:
The data for different antibodies against herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were obtained from the IEU GWAS database (https://gwas.mrcieu.ac.uk/datasets/), and the data for IPF were obtained from the Finngen GWAS database (https://r7.finngen.fi/). We selected eligible single nucleotide polymorphisms (SNPs) from summary-level data of GWAS as instrumental variables. The Generalized Summary data-based MR (GSMR) method was used as the main analysis method, complemented by inverse-variance weighted (IVW), MR-Egger, and weighted median analyses. Sensitivity analyses were conducted to check the robustness of the MR results, and reverse MR analyses were performed to assess the presence of reverse causality.

Results:
We found that the levels of antibodies against the EBV viral capsid antigen (VCA) p18 were associated with an increased risk of IPF. GSMR and IVW results indicate that anti-EBV IgG levels were significantly negatively associated with IPF. Sensitivity analyses confirmed the robustness of our results.

Conclusions:
Our results indicate that EBV infection increases the risk of IPF. Our findings enhance the understanding of the etiology of IPF. Targeting EBV infection may aid in the prevention and treatment of IPF.