title: Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health.
abstract: 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.
authors: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors: Usman
authors: U
authors: Ahmed
authors: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors: Attia
authors: A
authors: Anwar
authors: 1] Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K. [2] Warwick Systems Biology Centre, Coventry House, University of Warwick, Coventry CV4 7AL, U.K.
authors: Richard S
authors: RS
authors: Savage
authors: 1] Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K. [2] Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, U.K.
authors: Matthew L
authors: ML
authors: Costa
authors: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors: Nicola
authors: N
authors: Mackay
authors: 1] Sandwell and West Birmingham Hospital NHS Trust, Dudley Road, Birmingham B18 7QH, West Midlands, U.K. [2] Centre for Translational Inflammation Research, University of Birmingham, Birmingham B15 2TT, U.K.
authors: Andrew
authors: A
authors: Filer
authors: 1] Sandwell and West Birmingham Hospital NHS Trust, Dudley Road, Birmingham B18 7QH, West Midlands, U.K. [2] Centre for Translational Inflammation Research, University of Birmingham, Birmingham B15 2TT, U.K.
authors: Karim
authors: K
authors: Raza
authors: 1] Ipswich Hospital NHS Trust, Ipswich IP4 5PD, Suffolk, U.K. [2] Medical School, University of East Anglia, Norwich, NR4 7TJ U.K.
authors: Richard A
authors: RA
authors: Watts
authors: University of Exeter Medical School, St Luke's Campus, Exeter EX1 2LU, U.K.
authors: Paul G
authors: PG
authors: Winyard
authors: University of Exeter Medical School, St Luke's Campus, Exeter EX1 2LU, U.K.
authors: Joanna
authors: J
authors: Tarr
authors: 1] University of Exeter Medical School, St Luke's Campus, Exeter EX1 2LU, U.K. [2] Department of Rheumatology, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
authors: Richard C
authors: RC
authors: Haigh
authors: 1] Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K. [2] Warwick Systems Biology Centre, Coventry House, University of Warwick, Coventry CV4 7AL, U.K.
authors: Paul J
authors: PJ
authors: Thornalley
authors: 1] Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K. [2] Warwick Systems Biology Centre, Coventry House, University of Warwick, Coventry CV4 7AL, U.K.
authors: Naila
authors: N
authors: Rabbani
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000175:diagnosis*; D010003:Osteoarthritis / Q000175:diagnosis*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D002956:Citrulline; D006909:Hydroxyproline