Unveiling the Lipidome of Extracellular Vesicles in Joint Disorders: an avenue towards clinical applications

Abstract

Arthritis occurs when joints become inflamed, leading to symptoms like pain and stiffness. The primary forms are osteoarthritis (OA), characterized by low-grade inflammation and gradual degeneration, and more fulminant autoimmune conditions like rheumatoid arthritis (RA) and spondyloarthritis (SpA). Arthritis is very common in humans and horses and the comparable joint architecture of both species, makes of horses a good model for humans. Joint fluid lubricates and nourishes the joint. In this fluid numerous biological compounds are found, among which so-called “extracellular vesicles” (EVs). EVs are released by cells and composed of a lipid membrane and cargo molecules, such as proteins or RNA, for communication between cells. EVs have great potential as biomarkers, however, most studies focus on cargo only and ignore the lipids. In this thesis, we showed a correlation between the lipid and protein composition that changes according to the degree of OA, demonstrating the potential of EVs as composite biomarkers. We also identified that during the inflammatory peak of acute synovitis in horses, a specific lipid class, which is derived from neutrophils, the major invading cell in the joint during inflammation, becomes predominant. Similarly, in human neutrophil-derived EVs, a related, slightly different lipid class was predominant, which was also found in EVs from joint fluid of RA and SpA patients. We anticipate that further EV characterization may lead to the identification of new EV-biomarkers. Our results offer important insights into the potential of EV lipid-related biomarkers in arthritis and the role of neutrophil-related inflammation.