Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health

被引:53
作者
Ahmed, Usman [1 ]
Anwar, Attia [1 ]
Savage, Richard S. [1 ,2 ]
Costa, Matthew L. [1 ,9 ]
Mackay, Nicola [1 ]
Filer, Andrew [3 ,4 ]
Raza, Karim [3 ,4 ]
Watts, Richard A. [5 ,6 ]
Winyard, Paul G. [7 ]
Tarr, Joanna [7 ]
Haigh, Richard C. [7 ,8 ]
Thornalley, Paul J. [1 ,2 ]
Rabbani, Naila [1 ,2 ]
机构
[1] Univ Warwick, Univ Hosp, Clin Sci Res Labs, Warwick Med Sch, Coventry CV2 2DX, W Midlands, England
[2] Univ Warwick, Warwick Syst Biol Ctr, Coventry CV4 7AL, W Midlands, England
[3] Sandwell & West Birmingham Hosp NHS Trust, Birmingham B18 7QH, W Midlands, England
[4] Univ Birmingham, Ctr Translat Inflammat Res, Birmingham B15 2TT, W Midlands, England
[5] Ipswich Hosp NHS Trust, Ipswich IP4 5PD, Suffolk, England
[6] Univ E Anglia, Sch Med, Norwich NR4 7TJ, Norfolk, England
[7] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England
[8] Royal Devon & Exeter NHS Fdn Trust, Dept Rheumatol, Exeter, Devon, England
[9] Univ Warwick, Warwick Clin Trials Unit, Coventry CV4 7AL, W Midlands, England
关键词
SYNOVIAL-FLUID; HYDROXYPROLINE; ANTIBODIES; PROTEINS; METHYLGLYOXAL; PERFORMANCE; PROLINE; GLYOXAL; MARKERS; SERUM;
D O I
10.1038/srep09259
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.
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页数:7
相关论文
共 33 条
[1]
Developments in the scientific understanding of osteoarthritis [J].
Abramson, Steven B. ;
Attur, Mukundan .
ARTHRITIS RESEARCH & THERAPY, 2009, 11 (03)
[2]
[Anonymous], LC MS DRUG BIOANALYS, DOI DOI 10.1007/978-1-4614-3828-1_5
[3]
Analytical and diagnostic characteristics of 11 2nd- and 3rd-generation lmmunoenzymatic methods for the detection of antibodies to citrullinated proteins [J].
Bizzaro, Nicola ;
Tonutti, Elio ;
Tozzoli, Renato ;
Villalta, Danilo .
CLINICAL CHEMISTRY, 2007, 53 (08) :1527-1533
[4]
Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[5]
Autophagy Is a Protective Mechanism in Normal Cartilage, and Its Aging-Related Loss Is Linked With Cell Death and Osteoarthritis [J].
Carames, Beatriz ;
Taniguchi, Noboru ;
Otsuki, Shuhei ;
Blanco, Francisco J. ;
Lotz, Martin .
ARTHRITIS AND RHEUMATISM, 2010, 62 (03) :791-801
[6]
Connelly LB, 2006, DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION, P963
[7]
Almost all about citrulline in mammals [J].
Curis, E ;
Nicolis, I ;
Moinard, C ;
Osowska, S ;
Zerrouk, N ;
Bénazeth, S ;
Cynober, L .
AMINO ACIDS, 2005, 29 (03) :177-205
[8]
In vivo relevance of citrullinated proteins and the challenges in their detection [J].
De Ceuleneer, Marlies ;
Van Steendam, Katleen ;
Dhaenens, Maarten ;
Deforce, Dieter .
PROTEOMICS, 2012, 12 (06) :752-760
[9]
Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis Synovium in close association with tissue inflammation [J].
Foulquier, Celine ;
Sebbag, Mireille ;
Clavel, Cyril ;
Chapuy-Regaud, Sabine ;
Al Badine, Roula ;
Mechin, Marie-Claire ;
Vincent, Christian ;
Nachat, Rachida ;
Yamada, Michiyuki ;
Takahara, Hidenari ;
Simon, Michel ;
Guerrin, Marina ;
Serre, Guy .
ARTHRITIS AND RHEUMATISM, 2007, 56 (11) :3541-3553
[10]
Regularization Paths for Generalized Linear Models via Coordinate Descent [J].
Friedman, Jerome ;
Hastie, Trevor ;
Tibshirani, Rob .
JOURNAL OF STATISTICAL SOFTWARE, 2010, 33 (01) :1-22