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

TL;DR

This study found that proteins in extracellular vesicles from the blood of cutaneous lupus patients correlate with disease activity, offering potential biomarkers for monitoring the condition.

Contribution

The study identifies specific extracellular vesicle proteins in cutaneous lupus that correlate with disease activity, providing new insights into biomarker development.

Findings

Four proteins (mimecan, IFI27, fibulin-2, and snRNP B/B′) were uniquely present in CLE extracellular vesicles and increased with systemic lupus activity.

Lysozyme C and hyaluronan-binding protein 2 levels in EVs correlated with cutaneous disease activity but not systemic activity.

CLE EVs showed enrichment in antigen-presenting cell markers and proinflammatory proteins, suggesting a role in local inflammation.

Abstract

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.

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