Endothelial Cell Proteins as Biomarkers in Susac Syndrome

Abstract

ABSTRACT Objective 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. Methods 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. Results Six endothelial‐associated proteins demonstrated differential abundance in SS ( p < 0.05 on unadjusted analysis). Low‐density lipoprotein receptor‐related protein 1 was increased (log 2 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 (log 2 fold change −1.38 to −1.89; all p < 0.05). Conclusions 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. Trial Registration ClinicalTrials.gov, NCT00001248 and NCT02435810