Serum biomarker panel for the diagnosis of rheumatoid arthritis

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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.

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Most cited references 35

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2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

Daniel Aletaha, Tuhina Neogi, Alan J Silman … (2010)

The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."

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Rheumatoid arthritis

Anne Barton, Kazuhiko Yamamoto, Vibeke Strand … (2018)

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints and is associated with autoantibodies that target various molecules including modified self-epitopes. The identification of novel autoantibodies has improved diagnostic accuracy, and newly developed classification criteria facilitate the recognition and study of the disease early in its course. New clinical assessment tools are able to better characterize disease activity states, which are correlated with progression of damage and disability, and permit improved follow-up. In addition, better understanding of the pathogenesis of RA through recognition of key cells and cytokines has led to the development of targeted disease-modifying antirheumatic drugs. Altogether, the improved understanding of the pathogenetic processes involved, rational use of established drugs and development of new drugs and reliable assessment tools have drastically altered the lives of individuals with RA over the past 2 decades. Current strategies strive for early referral, early diagnosis and early start of effective therapy aimed at remission or, at the least, low disease activity, with rapid adaptation of treatment if this target is not reached. This treat-to-target approach prevents progression of joint damage and optimizes physical functioning, work and social participation. In this Primer, we discuss the epidemiology, pathophysiology, diagnosis and management of RA.

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Cytokine pathways and joint inflammation in rheumatoid arthritis.

E. Choy, G Panayi (2001)

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Author and article information

Contributors

Hee-Gyoo Kang:

ORCID: http://orcid.org/0000-0001-8690-2483

kanghg@eulji.ac.kr

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 18 January 2021

Publication date PMC-release: 18 January 2021

Publication date (Print): 2021

Volume: 23

Electronic Location Identifier: 31

Affiliations

[1 ]GRID grid.255588.7, ISNI 0000 0004 1798 4296, Department of Biomedical Laboratory Science, College of Health Sciences, , Eulji University, ; Seongnam, Republic of Korea

[2 ]GRID grid.255588.7, ISNI 0000 0004 1798 4296, Department of Biomedical Laboratory Science, College of Health Sciences, , Eulji University, ; Daejeon, Republic of Korea

[3 ]GRID grid.255588.7, ISNI 0000 0004 1798 4296, Department of Preventive Medicine, School of Medicine, , Eulji University, ; Daejeon, Republic of Korea

[4 ]GRID grid.412965.d, ISNI 0000 0000 9153 9511, Liberal Arts, , Woosuk University, ; Jeonju, Republic of Korea

[5 ]GRID grid.255588.7, ISNI 0000 0004 1798 4296, Division of Rheumatology, Department of Medicine, , Eulji University School of Medicine, ; Daejeon, Republic of Korea

Author information

Hee-Gyoo Kang http://orcid.org/0000-0001-8690-2483

Article

Publisher ID: 2405

DOI: 10.1186/s13075-020-02405-7

PMC ID: 7812661

PubMed ID: 33461622

SO-VID: 88c57b48-b1de-46bf-b8a7-9c64393df252

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 30 October 2020

Date accepted : 22 December 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;

Award ID: 2016M3A9B694241

Award Recipient : Hee-Gyoo Kang

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: rheumatoid arthritis,angiotensinogen,biomarkers,serum amyloid a-4 protein,retinol-binding protein-4,vitamin d-binding protein

Data availability:

ScienceOpen disciplines: Orthopedics

Keywords: rheumatoid arthritis, angiotensinogen, biomarkers, serum amyloid a-4 protein, retinol-binding protein-4, vitamin d-binding protein

Serum biomarker panel for the diagnosis of rheumatoid arthritis

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Abstract

Background

Methods

Results

Conclusions

Related collections

Orthopedics

Most cited references 35

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

Rheumatoid arthritis

Cytokine pathways and joint inflammation in rheumatoid arthritis.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

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Custom metadata

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