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

Area of Science:

• Neuroimmunology
• Neuroimaging
• Systems Biology

Background:

• Autoimmune thyroid diseases (AITD) are systemic conditions often linked to neurological issues.
• The precise neural and immunological mechanisms underlying these neurological manifestations are not well understood.
• Thyroid eye disease (TED) serves as a key model to investigate these neuroimmune connections.

Purpose of the Study:

• To investigate the neural mechanisms and brain-immune interactions in thyroid eye disease (TED).
• To identify specific brain regions and biological pathways affected in TED.
• To validate neuroimaging findings with peripheral immune data.

Main Methods:

• Combined resting-state functional magnetic resonance imaging (rs-fMRI) from a retrospective cohort of 116 TED patients with Allen Human Brain Atlas transcriptomic data.
• Integrated rs-fMRI data with regional transcriptomic profiles for transcriptional inference.
• Validated key findings in an independent prospective cohort (39 TED patients, 42 healthy controls) using rs-fMRI and peripheral blood RNA sequencing.

Main Results:

• Significant alterations in brain activity were observed in frontal, parietal, subcortical, and brainstem regions in TED patients.
• Enriched pathways related to synaptic signaling, neurovascular regulation, and immune activation were identified.
• Significant associations were found between immune cell infiltration and neural activity patterns, particularly involving the cortex and neurons.

Conclusions:

• The study delineates coordinated brain-immune associations in thyroid eye disease (TED).
• Findings generate novel hypotheses regarding neuroimmune interactions in autoimmune thyroid diseases (AITD).
• This research provides a foundation for understanding the neurological impact of AITD.