Endothelial Cell Proteins as Biomarkers in Susac Syndrome

Susac syndrome (SS) is a rare CD8⁺ T cell-mediated microangiopathy affecting the brain, retina, and auditory labyrinth. Endothelial injury is thought to be a central mechanism; however, no circulating disease biomarkers are known. We performed targeted proteomic profiling to identify circulating endothelial-associated proteins as biomarkers in SS.

Serum from four cases with definite or probable SS and eight healthy controls was analyzed using data-independent acquisition mass spectrometry. Analyses were restricted to proteins with established endothelial cell surface or membrane association, and differential abundance was assessed using detection-based (Fisher's exact) and quantitative (probabilistic dropout analysis) modeling.

Six endothelial-associated proteins demonstrated differential abundance in SS (p < 0.05 on unadjusted analysis). Low-density lipoprotein receptor-related protein 1 was increased (log₂ fold change = +2.19, p = 0.0059), whereas Nectin-2, Melanoma cell adhesion molecule, Fatty acid transport protein 4, P-selectin, and Interleukin-6 signal transducer were decreased (log₂ fold change -1.38 to -1.89; all p < 0.05).

Our findings suggest circulating proteins on the endothelial cell surface or membrane as potential biomarkers for SS and support endothelial dysfunction as a central disease mechanism. This pilot study provides a rationale for validation in larger, longitudinal cohorts.

ClinicalTrials.gov, NCT00001248 and NCT02435810.