Abstract

Background Rheumatoid arthritis (RA) is an autoimmune disease that starts with inflammation of the synovial membrane. Studies have been conducted to develop methods for efficient diagnosis of RA and to identify the mechanisms underlying RA development. Blood samples can be useful for detecting disturbance of homeostasis in patients with RA. Nanoliquid chromatography-tandem mass spectrometry (LC-MS/MS) is an efficient proteomics approach to analyze blood sample and quantify serum proteins. Methods Serum samples of 18 healthy controls and 18 patients with RA were analyzed by LC-MS/MS. Selected candidate biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) using sera from 43 healthy controls and 44 patients with RA. Results Thirty-eight proteins were significantly differentially expressed by more than 2-fold in healthy controls and patients with RA. Based on a literature survey, we selected six candidate RA biomarkers. ELISA was used to evaluate whether these proteins effectively allow distinguishing patients with RA from healthy controls and monitoring drug efficacy. SAA4, gelsolin, and vitamin D-binding protein were validated as potential biomarkers of RA for screening and drug efficacy monitoring of RA. Conclusions We identified a panel of three biomarkers for RA which has potential for application in RA diagnosis and drug efficacy monitoring. Further, our findings will aid in understanding the pathogenesis of RA.

Highlights

  • Rheumatoid arthritis (RA) causes inflammation of the synovial membrane that is surrounded by the joint capsule and is one of the intractable, rare diseases [1]

  • 1657 peptides and 184 proteins were identified in healthy controls, and 1468 peptides and 191 proteins were identified in RA patients

  • The results showed that vitamin D-binding protein is specific for female subjects, and serum amyloid A-4 level increased in patients with RA compared with the healthy controls, regardless of the sex

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Summary

Introduction

RA causes inflammation of the synovial membrane that is surrounded by the joint capsule and is one of the intractable, rare diseases [1]. Disease activity score 28 (DAS 28) is used to measure disease activity of RA by several criteria such as CRP and ESR Because they are general markers of inflammation, they are not specific to RA. Serum samples of 18 healthy controls and 18 patients with RA were analyzed by LC-MS/MS. Selected candidate biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) using sera from healthy controls and patients with RA. ELISA was used to evaluate whether these proteins effectively allow distinguishing patients with RA from healthy controls and monitoring drug efficacy. SAA4, gelsolin, and vitamin D-binding protein were validated as potential biomarkers of RA for screening and drug efficacy monitoring of RA. We identified a panel of three biomarkers for RA which has potential for application in RA diagnosis and drug efficacy monitoring. Our findings will aid in understanding the pathogenesis of RA

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