Proteomics Analysis for Verification of Rheumatoid Arthritis Biomarker Candidates Using Multiple Reaction Monitoring.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease in which autoantibodies attack the synovial membrane, causing joint inflammation. Blood tests would offer a powerful, minimally invasive method for early diagnosis of RA. However, no reliable biomarkers for RA are presently available. The aim is to develop biomarkers for RA by multiple reaction monitoring (MRM)-based quantification of candidate biomarkers. Proteomics approaches are commonly used to identify and verify disease biomarkers. For discovery of biomarkers for RA, SWATH acquisition is performed and selected candidate biomarkers are validated by MRM. Target serum proteins are compared between patients with RA and healthy controls divided into three groups based on rheumatoid factor level. A total of 45 differentially expressed proteins are identified, as determined by SWATH acquisition. Of these, 13 proteins are selected as novel candidate biomarkers. A total of five proteins (transthyretin, gelsolin, angiotensinogen, lipopolysaccharide-binding protein, and protein S100-A9) are shown to have the potential to distinguish patients with RA from healthy controls. These five proteins may improve the efficiency of diagnosis of RA. MRM can be used to easily diagnose RA by detecting five proteins simultaneously in a single sample with high sensitivity.