Systemic Proteomic Analysis Reveals Distinct Exosomal Protein Profiles in Rheumatoid Arthritis.
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ABSTRACT: Objective
Rheumatoid arthritis (RA) is a complex disease with unknown pathogenesis. In recent years, fewer have paid attention to the broad spectrum of systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA.Methods
Totally, 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 exosomal profiles.Results
A 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). Bioinformatics analysis revealed that transthyretin (TTR), angiotensinogen (AGT), lipopolysaccharide-binding protein (LBP), monocyte differentiation antigen CD14 (CD14), cartilage oligomeric matrix protein (COMP), serum amyloid P (SAP/APCS), and tenascin (TNC) can interact with each other. Subsequently, these cross-linked proteins may be mainly involved in the inflammatory-related pathways to mediate the onset of RA. Noteworthy, the LBP/CD14 complex can promote the expression of IL-8 and TNF-α, eventually leading to the development of RA.Conclusions
Our findings suggest distinct plasmatic 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.
SUBMITTER: Qin Q
PROVIDER: S-EPMC8390169 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neutrophil Extracellular Traps (NETs) are chromatin-derived extracellular structures that are expelled from neutrophils in response to infectious or inflammatory stimuli. NET DNA structures are decorated with proteins including histones, myeloperoxidase and neutrophil elastase. NETs are implicated in the development of auto-immunity in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) through the externalisation of intracellular neoepitopes e.g. dsDNA and nuclear proteins in SLE and citrullinated peptides in RA. The aim of this work was to use quantitative proteomics to identify and measure NET proteins produced by neutrophils from healthy individuals, and from patients with RA and SLE.
2019-02-18 | PXD011796 | Pride
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