Abstract
BackgroundTo understand the roles of serum exosomes in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of serum exosomes in patients with RA.MethodsExosomes were isolated from serum samples obtained from 33 patients (12 with active RA [aRA], 11 with inactive RA [iRA], 10 with osteoarthritis [OA]) and 10 healthy donors (HLs). Proteins extracted from the exosomes were separated by two-dimensional differential gel electrophoresis (2D-DIGE) and identified by mass spectrometry.ResultsIn total, 204 protein spots were detected by 2D-DIGE. In the aRA, iRA, and OA groups, 24, 5, and 7 spots showed approximately ≥ ±1.3-fold intensity differences compared with the HL group, respectively. We were able to identify proteins in six protein spots. Among them, the protein spot identified as Toll-like receptor 3 (TLR3) showed approximately 6-fold higher intensity in the aRA group than in the other groups.ConclusionsPatients with active RA possessed considerably different protein profiles of serum exosomes from patients with iRA, patients with OA, and healthy donors. The unique protein profile of serum exosomes, such as the possession of abundant TLR3 fragments, may reflect the pathophysiology of active RA.
Highlights
To understand the roles of serum exosomes in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of serum exosomes in patients with RA
We found that the serum exosomes in patients with active RA possessed considerably different protein profiles from those in patients with inactive RA, patients with osteoarthritis (OA), and healthy donors (HLs)
No significant differences were found between the active RA (aRA) and inactive RA (iRA) groups with regard to age, sex, disease duration, and test items other than markers for inflammatory condition (Table 1)
Summary
To understand the roles of serum exosomes in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of serum exosomes in patients with RA. Exosomes are nanometer-sized (50–100 nm) membranous extracellular vesicles secreted from various types of cells [1]. Exosomes are initially generated by inward budding of late endosomes, called “multivesicular bodies (MVBs)”, in cells and released from the cells by the fusion of MVBs with plasma membranes [1]. Exosomes play roles in the presentation of antigens to T cells [4]. Exosomes derived from antigen-presenting cells (APCs) were reported to possess. Tumor-derived exosomes were reported to induce T cell apoptosis via Fas ligand [9] and to inhibit interleukin (IL)-2-induced proliferation of T cells [10]. Exosomal programmed death-ligand 1 (PD-L1) was shown to inhibit the function of CD8+ T cells and facilitate the progression of melanoma [11]
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