Abstract
BackgroundRheumatoid arthritis (RA) is an autoimmune disease of inflammatory joint damage, wherein C-reactive protein and autoantibodies including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are rapidly elevated. These serological factors are diagnostic markers of RA; however, their sensitivity and specificity for prediction warrant improvement for an early and accurate diagnosis.MethodsWe aimed to identify alternative biomarkers by serum protein profiling using LC-MS/MS. We performed statistical and functional analysis of differentially expressed proteins to identify biomarker candidates complementing conventional serological tests.ResultsSeven biomarker candidates were verified through multiple reaction monitoring-based quantitative analysis, of which angiotensinogen (AGT), serum amyloid A-4 protein (SAA4), vitamin D-binding protein (VDBP), and retinol-binding protein-4 (RBP4) had an area under the curve over 0.8, thus distinguishing RA patients, including seronegative (RF- and anti-CCP-negative) RA patients, from healthy controls.ConclusionsTherefore, among seronegative RA patients, a four-biomarker panel (AGT, SAA4, VDBP, and RBP4) can prevent false negatives and help diagnose RA accurately.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease of inflammatory joint damage, wherein Creactive protein and autoantibodies including rheumatoid factor (RF) and anti-cyclic citrullinated peptide are rapidly elevated
Healthy controls were distinguished from RA patients (Fig. 1a)
Analysis of individual serum samples revealed differentially expressed proteins in the two groups, among which, AGT, retinol-binding protein-4 (RBP4), serum amyloid A-4 protein (SAA4), and vitamin D-binding protein (VDBP) emerged as novel diagnostic biomarkers on MRM absolute quantification, and their area under the curve (AUC) value was over 0.8, indicating a high diagnostic efficiency
Summary
Rheumatoid arthritis (RA) is an autoimmune disease of inflammatory joint damage, wherein Creactive protein and autoantibodies including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are rapidly elevated. These serological factors are diagnostic markers of RA; their sensitivity and specificity for prediction warrant improvement for an early and accurate diagnosis. Genetic factors account for 60% of the RA risk factors. These genetic factors include gene polymorphisms, epigenetic factors including DNA methylation and histone acetylation, and complex factors [2,3,4]. The disease is initially characterized by an inflammatory response, followed by autoantibody activation and damage to the synovial membrane and joints. To improve the efficiency of RA diagnosis, anti-CCP is used
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