Causal relationship between IgG N-glycosylation and autoimmune thyroid diseases, and the possible mediating role of immune cells and inflammatory cytokines

作者：Wenhua Li, Dongni Fan, D. H. Wei, Wei Wei, Ying Zhang, Min Yi · 发表于：Medicine · 年份：2025 · DOI：10.1097/md.0000000000045649 · 研究领域：Glycosylation and Glycoproteins Research、Monoclonal and Polyclonal Antibodies Research、Thyroid Disorders and Treatments

Immunoglobulin G N-glycans have been associated with the risk of autoimmune thyroid diseases (AITD). In the present study, we investigated the potential causal relationship between IgG N-glycosylation and AITD risk. Employing 2-sample Mendelian randomization (MR) and mediation analysis, we evaluated the causal associations between IgG N-glycosylation and 4 types of AITD, Graves' disease, autoimmune thyroiditis, autoimmune hyperthyroidism and autoimmune hypothyroidism - using genome-wide association study summary data. Fifteen IgG N-glycan traits were found to have causal relationships with AITD. Moreover, upon considering inflammatory cytokines and immune cell phenotypes as outcomes, 6 inflammatory cytokines and 14 immune cell phenotypes exhibited significant causal relationships with IgG N-glycan traits. Subsequent mediation analyses using 2-step MR revealed that "CD25 on CD24+ CD27+ B cells" mediated the causal association between IGP11 and GD, "HLA DR+ T cell%lymphocyte" mediated the causal association between IGP59 and autoimmune thyroiditis, and "B_NGF" mediated the causal association between IGP59 and autoimmune hyperthyroidism. However, further validation through using multivariable Mendelian randomization (MVMR) indicated that only B_NGF played a mediating role in the causal relationship between IGP59 and autoimmune hyperthyroidism, as other 2 mediators did not yield significant results. This MR study comprehensively assessed the interrelationships among IgG glycosyla...