Transcriptomic and Neuroimaging Decoding of Brain‐Immune Crosstalk in Thyroid Eye Disease

Autoimmune thyroid diseases (AITD) are systemic conditions frequently associated with neurological manifestations, yet the underlying neural and immunological mechanisms remain unclear. This study focuses on thyroid eye disease (TED), a representative AITD, to provide a deeper insight into its neural mechanism. We first combined resting-state functional magnetic resonance imaging (rs-fMRI) data from a retrospective cohort of 116 TED patients with transcriptomic data from the Allen Human Brain Atlas. The analysis of rs-fMRI data demonstrated significant alterations in frontal, parietal, subcortical, and brainstem regions in TED. By integrating rs-fMRI data with regional transcriptomic profiles derived from the postmortem Allen Human Brain Atlas, enabling region-level transcriptional inference, we revealed enriched pathways related to synaptic signaling, neurovascular regulation, and immune activation. Tissue and cellular level enrichment further showed close association with the cortex and neurons. Key neuroimaging findings identified in the retrospective cohort were subsequently validated in an independent prospective cohort of TED patients and healthy controls (TED: 39; HC: 42) using paired rs-fMRI and peripheral blood RNA sequencing data, which identified significant associations between immune cell infiltration and neural activity patterns. Collectively, these findings delineate coordinated brain-immune associations in TED and generate hypotheses regarding neuroimmune interactions in AITD.