Vitamin D Modulates Humoral Responses to SARS-CoV-2 Vaccination in Autoimmune Thyroiditis: An Endocrine-Immune Perspective Supported by Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

内容摘要

Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine-immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti-spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D3 related molecular targets were integrated with AIT-associated genes, followed by protein-protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D3 (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D3 to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine-immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance.