Single-cell multiomic analysis unveils the immune landscape dynamics of graves' ophthalmopathy

Graves' ophthalmopathy (GO) is an autoimmune disease that occurs concurrently with Graves' disease, potentially leading to facial disfigurement and irreversible vision loss. However, the molecular characteristics of cellular changes in the peripheral immune environment of GO patients remain unclear. This study presents a multi-omics single-cell analysis of peripheral blood from GO patients and healthy controls, revealing key molecular alterations in immune cell subpopulations. We identify increased chromatin accessibility and regulatory activity of pro-inflammatory factors, such as FOS and NF-κB family. Immune repertoire analysis shows enhanced diversity in GO patients. Notably, GO-specific clonal expansions are enriched in CD8 effector T (CD8 Te) cells, which exhibit signs of enhanced T cell chemotaxis and exhaustion. Multi-omics integration analysis reveals that changes in SLC35G1 and IDNK expression in CD8 Te are linked to disease phenotypes, with trends aligning with experimental results. We find that this cell cluster could infiltrate into orbital tissues and upregulate fibrosis-related pathways associated with fibroblasts in GO. These findings indicate its potential role in driving disease progression. Our study reveals the epigenetic and transcriptomic landscape in the peripheral blood of GO patients, enhancing the understanding of the pathogenic molecular mechanisms and offering potential directions for prevention and treatment.