Background/Purpose: Exosomes
are 60–150 nm membrane vesicles that are secreted by various cells into
surrounding body fluids including blood and urine. As vehicles for
intercellular communication, they are involved in immune cell activation. To
date, the role of exosomes in pathogenesis of systemic lupus erythematosus
(SLE) hasve not been fully elucidated. This
study was aimed to investigate as to whether exosome formation is increased and
whether they effectively contribute to proinflammatory cytokine response in
patients with SLE.

Methods:
Serum samples from SLE
patients, rheumatoid arthritis (RA) patients and healthy controls were obtained
at Seoul National University Hospital. Exosomes were isolated from sera using
ExoQuick and quantified using EXOCET. Healthy peripheral blood mononuclear
cells (PBMCs) were stimulated with exosomes from SLE patients, RA patients or
healthy controls. After 24 hours, production of interferon (IFN)-a,
interleukin (IL)-1b, IL-6, and tumor
necrosis factor (TNF)-a were measured using ELISA. Correlation between SLE disease activity
index (SLEDAI) and exosome levels was assessed by Spearman correlation.

Results:
The purified exosomes
were 60-150nm in size and had a membrane bilayer on electron microscopy.
Exosomes from SLE induced healthy PBMCs to produce
high levels of IFN-a, IL-1b,
IL-6, and TNF-a, whereas exosomes derived from RA patients or healthy controls did
not (Figure 1). Exosome-depleted SLE serum and SLE exosomes that were
mechanically disrupted fail to elicit any significant proinflammatory cytokine
production. The serum levels of
exosomes were significantly higher in SLE patients than healthy controls
(21.13×10⁷±3.711
x10⁷ vs. 110.4 x10⁷±20.62 x10⁷,
p=0.037) and their levels correlated with SLEDAI in patients with SLE
(r=0.3663, p=0.0371).

Conclusion:
These data suggest that
exosomes are generated and they contribute to proinflammatory response in
patients with SLE. Exosomes might serve as a novel biomarker of disease
activity. Treatment targeting exosome might offer a new therapeutic option.

Figure 1.
Production of proinflammatory cytokines IFN-a
(A), TNF-a(B),
IL-1b
(C), and IL-6 (D) by the healthy PBMCs after stimulation with exosomes from HC or
SLE patients. Data are presented as the mean±SEM.
* p<0.05; ** p<0.01