Unlocking clues to rheumatoid arthritis through extracellular vesicles

in Publications April 8, 2025

A new study led by researchers at Oslo University Hospital offers a deeper look into how tiny particles in the blood—called extracellular vesicles (EVs)—may play a role in rheumatoid arthritis (RA). EVs are like molecular “mail carriers” that shuttle proteins and other signals between cells, and they’ve gained attention as potential biomarkers for disease detection and monitoring.

What sets this study apart is that the researchers focused on newly diagnosed RA patients who had not yet started treatment. This avoids the confounding effects of medications on the results. The team compared blood plasma from 32 RA patients and 20 healthy individuals, enriching the EVs using size exclusion chromatography and analyzing their protein content with high-resolution proteomics.

The findings were striking: RA patients had more EVs, and their EVs were larger than those found in healthy controls. Among the 682 proteins identified in these vesicles, 26 were significantly increased and 31 were decreased in RA patients. Many of these proteins are linked to inflammation and immune system activity—including SAA1 and S100A9, two proteins already suspected to play a role in RA.

Potential cell and tissue origin of RA associated EV proteins

The plot highlights our main findings as reported by gene expression across cell and tissue types in the Human Protein Atlas and the proteins’ corresponding fold-change and adjusted p-values detected in our DE analysis.

Interestingly, the researchers found that these EV proteins didn’t correlate with the total levels of those same proteins in the blood serum. This suggests that EVs may act as a specialized delivery system for inflammatory molecules, making them especially valuable for understanding disease mechanisms and identifying early biomarkers.

These insights could lead to better diagnostic tools and a deeper understanding of how inflammation spreads in autoimmune diseases like RA. It also highlights the importance of studying EVs not just as bystanders, but as active players in disease.

Rydland A, Heinicke F, Nyman T A, Trøseid A S, Flåm S T, Stensland M, Gehin J, Eikeland J, Øvstebø R, Mjaavatten M D, Lie B A. (2025) Newly-diagnosed rheumatoid arthritis patients have elevated levels of plasma extracellular vesicles with protein cargo altered towards inflammatory processes. Scientific Reports 15(1):11632. [article]