Objectives: Vogt-Koyanagi-Harada syndrome is common autoimmune uveitis
that can cause blindness. Recent studies have shown that plasma exosomes carry
disease-related proteins that may serve as biomarkers. Here, we aimed to find
candidate biomarkers of Vogt-Koyanagi-Harada disease using proteomic analysis of
Methods: Exosomes were isolated from the plasma of normal controls and Vogt-
Koyanagi-Harada patients in the following groups: a) initial inflammatory attack (active
stage), b) remission after one month of treatment (unstable stage), and c) stationary
phase after three months of treatment (stable stage). Groups were analyzed by mass
spectrometry using isobaric tags for relative and absolute quantitation. After functional
analysis, proteins of interest were verified by ELISA.
Results: 463 proteins were identified in the exosomes. Forty-three were upregulated at
the active inflammation stage, including inflammation-associated proteins. Thirty-one
were downregulated. Gene ontology and pathway analyses revealed differential proteins
related to cell adhesion, cell phagocytosis, cytoskeleton movement, leukocyte migration
across endothelial cells, and platelet activation. By ELISA, Carbonic anhydrase 2 and
Ras-related protein Rap-1b were verified as more plentiful at the active stage compared
to the normal control and stationary phase in exosomes, but not, however, in
microvesicles or plasma.
Conclusion: Plasma exosomes of Vogt-Koyanagi-Harada patients contain many
proteins related to the degree of inflammation. The levels of Carbonic anhydrase 2 and
Ras-related protein Rap-1b in exosomes can be used as biomarkers for active
inflammation in Vogt-Koyanagi-Harada disease. Further investigation could help study
the pathogenesis of Vogt-Koyanagi-Harada disease and identify therapeutic targets.