Abstract
BackgroundExosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA).MethodsThe study population consisted of 60 patients with RA: 30 in the clinical remission (CR) group with a Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) ≤2.6 and 30 in the non-clinical remission (non-CR) group with a DAS28-ESR >2.6. Preparation of exosomes from patient serum samples was performed with the ExoQuick kit, and protein identification/quantification was performed using tandem mass tag labeling/mass spectrometry and an enzyme-linked immunosorbent assay. Comparisons between groups were made using Student’s t test or the Mann-Whitney U test, as appropriate. Spearman’s correlation coefficients (ρ) were calculated.ResultsWe identified six candidate proteins. Exosomal levels of amyloid A (AA) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) differed between the CR and non-CR groups. Both serum and exosomal AA levels were higher in the non-CR group than in the CR group (p = 0.001). Significant positive correlations were found between exosomal AA and C-reactive protein (CRP) as well as between serum AA and CRP (ρ = 0.614, p = 0.001, and ρ = 0.624, p = 0.001, respectively). Although serum levels of LYVE-1 did not differ between the non-CR and CR groups, exosomal levels of LYVE-1 were lower in the non-CR group than in the CR group (p = 0.01). We identified positive correlations between serum/exosomal LYVE-1 and CRP only in the non-CR group (serum ρ = 0.376, p = 0.04; exosome ρ = 0.545, p = 0.002).ConclusionsExosomal LYVE-1 shows potential for use as an additional marker of disease activity in patients with RA, and exosomes may carry other useful markers for RA.
Highlights
Exosomes are thought to play an important role in exchanging information between cells
Transmembrane exosomal proteins directly interact with the signaling receptors of target cells, and exosomes fuse with the plasma membranes of recipient cells to deliver their contents, such as microRNAs, into the cytosol; this process is associated with the pathogenesis of various diseases [2]
Lee et al reported that circulating exosomes from patients with systemic lupus erythematosus (SLE) could induce healthy peripheral blood mononuclear cells to produce inflammatory cytokines, and exosome levels were correlated with disease activity in patients with SLE [4]
Summary
Exosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA). Exosomes have a protein and lipid composition that depends on their cellular origin and the state of activation, infection, and/or transformation of the parent cells. These proteins and lipids play roles in mediating inflammatory and autoimmune diseases. Vesicles derived from synovial fibroblasts of patients with rheumatoid arthritis (RA) have higher levels of a membrane-bound form of tumor necrosis factor (TNF) than vesicles from healthy control individuals [3]. Lee et al reported that circulating exosomes from patients with systemic lupus erythematosus (SLE) could induce healthy peripheral blood mononuclear cells to produce inflammatory cytokines, and exosome levels were correlated with disease activity in patients with SLE [4]
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