Genetically predicted immunoglobulin G N-glycan profiles as risk and protective factors in dermatitis

Dermatitis is a common inflammatory skin disorder that includes atopic, contact, infective, and seborrhoeic dermatitis, yet its underlying molecular mechanisms remain unclear. Immunoglobulin G (IgG) N-glycosylation, a post-translational modification influencing immune responses, has been implicated in inflammatory diseases, but its causal role in dermatitis is unknown. This study employed Mendelian randomization (MR) to investigate the relationship between IgG N-glycan profiles and dermatitis subtypes using genome-wide association study (GWAS) data from 8,090 European individuals and dermatitis datasets from the GWAS Catalog and FinnGen consortium. Genetic variants associated with IgG N-glycan traits were selected as instrumental variables (IVs), and causal effects were estimated using inverse variance-weighted (IVW) analysis, supported sensitivity analysis to assess pleiotropy and heterogeneity. The analysis identified GP18, GP2, and GP23 as significantly associated with atopic dermatitis, indicating a role in inflammatory pathways. GP20 was positively associated with infective dermatitis, suggesting involvement in immune defense against microbial infections. Conversely, GP20, GP2, and GP6 showed negative associations with seborrhoeic dermatitis, implying a potential protective role. GP4 was positively linked to contact dermatitis, highlighting IgG glycosylation’s role in allergic sensitization. These results provide the first causal evidence linking IgG N-glycan modifications to dermatitis, reinforcing the importance of glycosylation in immune regulation. Our findings suggest that IgG N-glycans could serve as biomarkers or therapeutic targets for dermatitis, paving the way for glycan-based interventions. Future studies should validate these findings across diverse populations and explore the underlying biological mechanisms driving IgG glycosylation-mediated immune modulation in dermatological diseases.