Proteomic insight into Susac syndrome utilising tear fluid - case study

Susac Syndrome (SuS) is a rare autoimmune neurovascular disorder characterised by sudden visual loss, hearing disturbances, and encephalopathy. Pathology affects the small vessels of the brain, retina, and inner ear. Diagnosing SuS is challenging due to its rarity, complexity, and nonspecific symptoms. This single-case study presents a proteomic analysis of tear fluid from a patient with SuS, revealing upregulated proteins involved in immune dysregulation, cytoskeletal remodelling, and cellular repair. The activation of inflammatory proteins (e.g., S100), cytoskeletal and motility-related proteins (e.g., ezrin, radixin), and membrane transport proteins (e.g., aquaporin-5, chloride intracellular channel protein), together with activation of MAPK and NF-κB signalling pathways, highlights immune dysregulation and neurovascular damage in SuS. Hyperactivation of the MAPK and NF-κB pathways leads to chronic neuroinflammation and decreased expression of neutrophil defensin 1, indicating a shift from a protective to a chronic inflammatory response. These findings from the personalized proteomic pattern of SuS support the potential of tear fluid proteomics for diagnosing SuS and offer valuable insights into its underlying molecular mechanisms.