Background Cutaneous lupus erythematous (CLE) is amanifestation 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.

Methods EVs were isolated from the plasma of 5 healthy controls, 6 CLE patients, and 17 dermatomyositis patients using sequential ultracentrifugation and size-exclusion chromatography (SEC). Surface markers were detected by MACSPlex bead flowcytometry. Protein content of the EVs was analyzed by mass spectrometry using LC-MS/MS.

Results EVs in blood are mainly derived from platelets, endothelial cells, and antigen-presenting cells. EVs from CLE patients’ blood contained 4 unique proteins:, Mimecan, Interferon alpha-inducible protein 27, Fibulin-2, and Small nuclear ribonucleoprotein-associated proteins B and B’ (antigens of anti-Sm antibodies). A number of these proteins were increased in patients with a high SLEDAI (SLE Disease Activity Index). 18 significantly upregulated and 15 downregulated proteins were detected in CLE EV compared with HC. A number of upregulated proteins demonstrated a positive correlation with the SLEDAI (r=0.79), but not with the cutaneous lupus erythematosus disease area and severity index (CLASI) (r=0.21). 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,

Conclusions 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 EV of CLE blood correlated with CLASI rather than SLEDAI, suggesting that the content of EV’s are different in SLE and CLE.