Plasma extracellular vesicles are not associated with the activity of systemic lupus erythematosus

Extracellular vesicles (EVs) are potential biomarkers of cell activation and injury, and it is crucial to clarify their role in systemic lupus erythematosus (SLE), an inflammatory, chronic, and autoimmune disease. This study aimed to investigate plasma EVs, derived from leukocytes and platelets, in patients with SLE using different EV detection methods. This is a cross-sectional study with 43 plasma samples obtained from patients with SLE and 13 samples from individuals without SLE (nSLE). Disease activity was determined by the SLE Disease Activity Index (SLEDAI-2K) and the use of immunosuppressant drugs was assessed. Plasma EVs were isolated by differential centrifugation and detected using nanoparticle tracking analysis (NTA) to identify the size and distribution profile of the nanoparticles, nanoscale flow cytometry as a reference method to identify the origin of the EVs, and in-house immunoenzymatic method (ELISA) to detect these plasma EVs. Among the SLE patients evaluated, 89.8% were female, with a median age of 42 (95%CI, 31-53) years old. In-house ELISA detected higher levels of platelet-derived EVs in SLE patients (p=0.001). However, the flow cytometry detected elevated levels of leukocyte-derived EVs in SLE patients (p=0.0009). ROC curve analysis showed a good performance of the in-house ELISA for platelet-derived EVs (AUC=0.8, p=0.01) in discriminating individuals with SLE. NTA showed a similar nanoparticle count and size profile between groups. We found no relationship between SLEDAI-2K and plasma EVs, but we identified elevated leukocyte-derived EVs counts (p=0.01) in patients on immunosuppressive therapy. Taken together, our results show that it is possible to detect EVs by ELISA and suggest that plasma EVs have a strong potential as biomarkers of inflammation in SLE, with a relationship between immunosuppression and the elevation of leukocyte-derived EVs, but they are not associated with SLEDAI-2K.