Extracellular Vesicular Proteins in Plasma from Patients with Cutaneous Lupus Correlate with Disease Activity

Cutaneous lupus erythematosus (CLE) can occur independently of lupus erythematosus. SLE, and its responsiveness to treatment, does not necessarily align with that of coexisting SLE. Extracellular vesicles (EVs) allow communication between cells and rapid delivery throughout the body. We hypothesized that EVs may support disease-specific inflammation in CLE and SLE patients. Plasma EVs from healthy controls (n = 5), CLE (n = 6), and dermatomyositis (n = 17) were purified by ultracentrifugation and size-exclusion chromatography, phenotyped by flow cytometry, and profiled by LC-MS/MS. Circulating EVs were mainly platelet-, endothelial-, and antigen-presenting cell-derived examples. CLE EVs harbored four proteins absent in the controls-mimecan, IFI27, fibulin-2, and snRNP B/B' (anti-Sm an-tigens)-and their cumulative number increased with SLEDAI. Relative to the controls, 18 proteins were upregulated and 15 downregulated in CLE EVs. The number of upregulated proteins showed a trend toward a correlation with SLEDAI (r = 0.79, p = 0.06) but not with CLASI (r = 0.21). Among upregulated proteins, lysozyme C and hyaluronan-binding protein 2 tracked with cutaneous activity (CLASI r = 0.74 and r = 0.86) but not with systemic activity (SLEDAI r = 0.52 and r = 0.31). CLE plasma EVs were enriched in antigen-presenting cell markers and disease-related cargo, including anti-Sm antigens and proinflammatory proteins. Although overall protein diversity correlated primarily with systemic disease activity, a subset of proteins appeared to reflect cutaneous activity.