# 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

## TL;DR

This study explores how vitamin D levels affect immune responses to SARS-CoV-2 vaccines in people with autoimmune thyroiditis, using both clinical data and molecular simulations.

## Contribution

The study reveals a novel link between vitamin D status and vaccine-induced antibody responses in autoimmune thyroiditis through integrated clinical and computational approaches.

## Key findings

- Lower vitamin D levels correlated with higher anti-RBD IgG antibody titers in autoimmune thyroiditis patients.
- Molecular docking and simulations showed vitamin D3 binding compatibility with key endocrine-related proteins like CYP19A1 and ESR1.
- Network pharmacology identified steroid hormone biosynthesis pathways as potential mediators of vitamin D's immunomodulatory effects.

## Abstract

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.