BackgroundRheumatoid arthritis (RA) is a heterogeneous and complex disease characterized by autoantibodies production and inflammation of the synovium. Its underlying mechanisms remain elusive. In recent years, exosomes have emerged as non-invasive biomarkers in diverse diseases. Due to its various inflammatory and immunological functions, some studies highlighted abnormalities of exosomes in RA, but fewer have paid attention to the broad spectrum of potential systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA using systemic proteomic method. MethodsTotally 12 specimens of plasma from 6 RA patients and 6 age-and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in exosomes. Gene ontology (GO), protein interaction network (PPI) and KEGG pathway analyses were used in subcellular localization analysis. ResultsA total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC≥2.0 and P<0.05) and 5 proteins were downregulated (FC≤0.5 and P<0.05). Most of these DEPs were immunoglobullins (Igs). Bioinformatics analysis indicated that these Igs are involved in inflammatory response of RA through diverse immune regulatory pathways, such as NF-kappa B signaling pathway. PPI analysis revealed that transthyretin (TTR, P02766), angiotensinogen (AGT, P01019), lipopolysaccharide-binding protein (LBP, P18428), monocyte differentiation antigen CD14 (CD14, P08571), cartilage oligomeric matrix protein (COMP, P49747), serum amyloid P (SAP/APCS, P02743) and tenascin (TNC, P24821) can interact with each other or may form a regulatory networks. Subsequently, these cross-linked proteins may mainly involve in the NF-kappa B signaling pathway or inflammatory-related pathways to mediate the onset of RA. Noteworthy, among these exosomal DEPs, the complex composed of LBP and CD14 is involved in NF-kappa B signaling pathway, resulting in promoted expression of IL-8, TNF-α, and eventually leading to the development of RA.ConclusionsOur findings suggest distinct plasmic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA, but also serve as novel biomarkers in RA diagnosis and prognosis.