112 Extracellular vesicular proteins in plasma from patients with cutaneous lupus correlate with disease activity

Cutaneous lupus erythematous (CLE) is a manifestation of systemic lupus erythematosus (SLE), that may have no systemic symptoms. SLE is known to affect a heterogeneous group of patients, and drug treatment response differs between each affected organ. Extracellular vesicles (EVs) have attracted attention as new communication tools between cells, that encapsulate various substances and deliver them rapidly throughout the body. We hypothesized that EVs might support disease specific inflammation in CLE and SLE. EVs were isolated using sequential ultracentrifugation and size- exclusion chromatography (SEC) from the plasma of 5 healthy controls, 6 CLE patients, and 17 dermatomyositis patients. Surface markers were detected by MACSPlex bead flow cytometry. Protein content of the EVs was analyzed by mass spectrometry using LC-MS/MS. EVs from CLE patients’ blood contained 4 unique proteins including antigens of anti-Sm antibodies. A number of these proteins were increased in patients with a high SLEDAI (SLE Disease Activity Index). Of the 18 proteins increased in CLE EVs, lysozyme C and hyaluronan-binding protein densities were positively correlated with CLASI (r=0.74 and r=0.86 respectively), but not with SLEDAI (r=0.52, r=0.31). EVs in the blood of CLE were abundantly derived from antigen-presenting cells, and contained disease-specific proteins such as anti-Sm antigens and pro-inflammatory proteins. The concentration of some of the proteins contained in EVs from CLE blood correlated with CLASI rather than SLEDAI, suggesting that the content of EV’s are different in SLE and CLE.