Abstract

Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.

Highlights

  • Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the joints and surrounding synovial membrane [1]

  • Because the expression pattern of serum proteins is altered in diseased conditions, such as RA, analysis of protein expression pattern and protein function has been used for biomarker discovery

  • Because blood is obtained from patients and reflects the overall status of patients, in contrast to other body fluids or urine, in our study, we obtained serum from patients with RA and tried to discover diagnostic biomarkers in informative blood samples using mass spectrometry

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Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the joints and surrounding synovial membrane [1]. Patients suspected to have RA show symptoms of morning stiffness, pain, and swelling, which continue over six weeks. It is comprehensively evaluated by serological tests for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) and for inflammatory markers such as CRP, an ESR test, and an imaging test [7]. Blood, urine, and body fluids such as synovial fluid may be used as the samples. Because blood is obtained from patients and reflects the overall status of patients, in contrast to other body fluids or urine, in our study, we obtained serum from patients with RA and tried to discover diagnostic biomarkers in informative blood samples using mass spectrometry

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