Causal effects of antibody-mediated immune responses on allergic diseases: A bidirectional Mendelian randomization study

Accumulating evidence indicates that microbial infections and their elicited immune responses may contribute to allergic disease pathogenesis, but the causal relationships remain unclear. We performed a bidirectional 2-sample Mendelian randomization (MR) study utilizing genome-wide association study summary statistics. We analyzed causal relationships between 46 antibody-mediated immune responses and 5 allergic diseases: allergic asthma (AA), allergic conjunctivitis, atopic dermatitis (AD), allergic rhinitis (AR), and allergic urticaria (AU). The primary analysis method was inverse-variance weighted, supplemented by MR-Egger, weighted median, and weighted mode methods. Robustness was assessed through tests for heterogeneity, pleiotropy, and leave-one-out sensitivity analysis. As an observational genetic methodology, MR estimates are subject to potential biases from pleiotropy. Thus, our findings suggest associations rather than definitive causation. Polyomavirus 2 JC VP1 antibody levels and Antihuman herpes virus 7 IgG seropositivity may influence the risk of AA disease. Toxoplasma gondii p22 antibody levels may confer protection against allergic conjunctivitis. Epstein-Barr virus EBNA-1 antibody levels are positively associated with AD, while Chlamydia trachomatis momp A antibody levels are negatively associated with AD. H pylori CagA antibody levels are positively linked to AR. Epstein-Barr virus EBNA-1 antibody levels are inversely related to AR. The positivity of H pylori Catalase antibody levels and herpes simplex virus 2 mgG-1 antibody levels are potential risk factors for AU. Antihuman herpes virus 6 IE1B IgG seropositivity may be a protective factor for AU. Reverse MR indicated that AA may elevate anti-H pylori IgG seropositivity. Sensitivity analyses confirmed robustness (P > .05). Our findings unveil potential causal links between antibody-mediated immune responses and allergic diseases, which may inform future mechanistic research and therapeutic strategies, highlighting the role of pathogen-immune interactions.