Proteomic analysis of extracellular vesicles reveals an immunogenic cargo in rheumatoid arthritis synovial fluid

Clinical & Translational Immunology
Andrew D FoersKen C Pang

Abstract

Extracellular vesicles (EVs) from rheumatoid arthritis (RA) synovial fluid (SF) have been reported to stimulate the release of pro-inflammatory mediators from recipient cells. We recently developed a size exclusion chromatography (SEC)-based method for EV isolation capable of high-quality enrichments from human SF. Here, we employed this method to accurately characterise the SF EV proteome and investigate potential contributions to inflammatory pathways in RA. Using our SEC-based approach, SF EVs were purified from the joints of RA patients classified as having high-level (n = 7) or low-level inflammation (n = 5), and from osteoarthritis (OA) patients (n = 5). Protein profiles were characterised by mass spectrometry. Potential contributions of EV proteins to pathological pathways and differences in protein expression between disease groups were investigated. Synovial fluid EVs were present at higher concentrations in RA joints with high-level inflammation (P-value = 0.004) but were smaller in diameter (P-value = 0.03) than in low-level inflammation. In total, 1058 SF EV proteins were identified by mass spectrometry analysis. Neutrophil and fibroblast markers were overrepresented in all disease groups. Numerous proteins with pot...Continue Reading

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Citations

Aug 18, 2021·The Journal of Clinical Investigation·Hui WangGeorge Hajishengallis
Oct 14, 2021·Database : the Journal of Biological Databases and Curation·Dan ShaoJuan Cui

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Datasets Mentioned

BETA
PXD015145

Methods Mentioned

BETA
size exclusion chromatography
transmission electron microscopy
electrophoresis
gel filtration
Protein Assay

Software Mentioned

Image Lab
NTA
EV
LFQAnalyst
pheatmap R package
Bioconductor package
limma
Andromeda
PEAKS
NetMHCII

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