Exploring the causal role of pathogen-derived antibodies in major urinary and kidney diseases: Insights from generalized summary data-based Mendelian randomization.

Abstract

Chronic kidney and urinary tract diseases, including glomerulonephritis, nephrotic syndrome, and chronic kidney disease (CKD), present significant global health challenges. Recent studies suggest a complex interplay between infectious pathogens and immune-mediated kidney damage. This study employs Generalized Summary data-based Mendelian Randomization (GSMR) to explore causal relationships between pathogen-derived antibodies and major urinary and kidney diseases.We conducted a two-sample MR analysis using summary statistics from large-scale Genome-Wide Association Studies (GWAS) to assess associations between 46 pathogen-specific antibodies and seven urinary system diseases. We utilized robust statistical methods, including inverse variance weighting, to ascertain causal effects while controlling for potential confounders.Significant associations were identified between several pathogen-specific antibodies and disease risk. Notably, Epstein-Barr virus (EBNA-1) antibody levels were inversely associated with glomerulonephritis and nephrotic syndrome, indicating a potential protective effect. Conversely, Anti-Merkel cell polyomavirus IgG seropositivity was linked to increased risks of CKD and glomerulonephritis. Additionally, immune-mediated mechanisms were highlighted, with certain antibodies exhibiting dual roles as risk factors or protective agents.This study underscores the complex role of pathogen antibodies in the pathogenesis of kidney and urinary tract diseases, revealing significant implications for future research and potential therapeutic strategies. The findings advocate for further investigation into specific pathogen interactions with the immune system, aiming to inform targeted interventions.