Sora Mun1, Jiyeong Lee2, Mira Park3, Jieun Shin4, Mi-Kyoung Lim5, Hee-Gyoo Kang6. 1. Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam, Republic of Korea. 2. Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Daejeon, Republic of Korea. 3. Department of Preventive Medicine, School of Medicine, Eulji University, Daejeon, Republic of Korea. 4. Liberal Arts, Woosuk University, Jeonju, Republic of Korea. 5. Division of Rheumatology, Department of Medicine, Eulji University School of Medicine, Daejeon, Republic of Korea. 6. Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam, Republic of Korea. kanghg@eulji.ac.kr.
Abstract
BACKGROUND: Rheumatoid 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. METHODS: We 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. RESULTS: Seven 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. CONCLUSIONS: Therefore, among seronegative RA patients, a four-biomarker panel (AGT, SAA4, VDBP, and RBP4) can prevent false negatives and help diagnose RA accurately.
BACKGROUND:Rheumatoid 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. METHODS: We 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. RESULTS: Seven 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 RApatients, including seronegative (RF- and anti-CCP-negative) RApatients, from healthy controls. CONCLUSIONS: Therefore, among seronegative RApatients, a four-biomarker panel (AGT, SAA4, VDBP, and RBP4) can prevent false negatives and help diagnose RA accurately.
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