476 Microvesicles Induce Pro-Inflammatory Cytokines in Dermatomyositis

Microvesicles (MVs) are micron-scale bilayer membrane vesicles released from almost all cell types under activation or apoptosis. They have been detected in various bodily fluids, organs, and tissues in different pathologic states. MVs harbor molecules from their parental cells, which may mediate intercellular communications, and are thought to play an important role in autoimmune inflammation as they have been shown to induce the synthesis of various pro-inflammatory cytokines in several immune cell types. Previous studies have demonstrated that circulating microvesicles are increased in a variety of autoimmune diseases, including dermatomyositis (DM). In the current study, we aim to characterize the induction of pro-inflammatory cytokines by MVs isolated from patients with dermatomyositis. Peripheral blood mononuclear cells (PBMCs) were isolated from eight DM patients and five healthy controls and subsequently stimulated with either no treatment, MVs isolated from the homologous plasma, or homologous MV-free plasma. The levels of TNFα, IFN-α, IL-6, and IL-8 secreted by the cells in the conditioned medium were then quantified with an enzyme-linked immunosorbent assay (ELISA). In DM patients, MVs significantly increased the cellular secretion of TNFα from homologous PBMCs compared to no treatment (p<0.05) and MV-free plasma (p<0.05). In the healthy controls, MVs did not significantly increase TNFα secretion from the homologous PBMCs compared to no treatment and MV-free plasma. MVs from DM patients significantly increased cellular secretion of IFN-, IL-6, and IL-8 compared to no treatment (p<0.05, p<0.001, p<0.001, respectively). Therefore, MVs from DM patients induce secretion of key immunostimulatory cytokines from their homologous immune cells, suggesting that MVs likely play a role in the pathogenesis of DM. In conclusion, our preliminary studies indicate that circulating MVs are important pro-inflammatory mediators that amplify pro-inflammatory responses in patients with DM.