Endothelial Cell Proteins as Biomarkers in Susac Syndrome

Area of Science:

• Immunology and Autoimmune Diseases
• Proteomics and Biomarker Discovery
• Vascular Biology and Endothelial Function

Background:

• Susac syndrome (SS) is a rare autoimmune microangiopathy affecting the brain, retina, and inner ear.
• The underlying mechanism involves CD8+ T cell-mediated endothelial injury, but no reliable biomarkers exist.
• Identifying circulating biomarkers is crucial for diagnosis and understanding SS pathogenesis.

Purpose of the Study:

• To identify circulating endothelial-associated proteins as potential biomarkers for Susac syndrome (SS).
• To investigate the role of endothelial dysfunction in the pathophysiology of SS.

Main Methods:

• Targeted proteomic profiling using data-independent acquisition mass spectrometry on serum samples.
• Analysis included four SS cases and eight healthy controls.
• Focused on proteins with known endothelial cell surface or membrane association, assessed by quantitative and detection-based modeling.

Main Results:

• Six endothelial-associated proteins showed differential abundance in SS patients compared to controls (p < 0.05).
• Low-density lipoprotein receptor-related protein 1 was significantly increased in SS.
• Nectin-2, Melanoma cell adhesion molecule, Fatty acid transport protein 4, P-selectin, and IL-6 signal transducer were significantly decreased in SS.

Conclusions:

• Circulating endothelial cell surface/membrane proteins are potential biomarkers for Susac syndrome.
• Findings support endothelial dysfunction as a central mechanism in SS.
• This pilot study warrants validation in larger, longitudinal cohorts for clinical application.