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.

Highlights

  • Rheumatoid arthritis (RA) is the most common systemic autoimmune disorder affecting approximately 0.5-1% of the adult population worldwide

  • All participants were Chinese in origin, and the samples in our study needed to be at fasting state when their whole blood were drawn

  • Our data once again demonstrated the important role of inflammatory processes in the pathogenesis of RA

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Summary

Introduction

Rheumatoid arthritis (RA) is the most common systemic autoimmune disorder affecting approximately 0.5-1% of the adult population worldwide. The disease is characterized by inflammation and proliferation of synovial tissue, destruction of cartilage and bone, and production of various autoantibodies [1] and often presents systemic manifestations including eye, skin, pulmonary, peripheral neuropathy, and cardiovascular events during progression [2]. The diagnosis of RA is mainly based on the clinical symptoms, imaging results, and some traditional laboratory tests. These methods are often used to diagnose RA during the middle-to-late disease period when treatments are unable to effectively control the disease progression [4]. As a complex and heterogeneous disease, about 30-40% of RA patients do not have a good response to an optimal dosing regimen of drugs including methotrexate (MTX). More efficient biomarkers need to be explored for early diagnosis and treatment of RA

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