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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.

Original publication

DOI

10.1038/srep09259

Type

Journal article

Journal

Scientific reports

Publication Date

19/03/2015

Volume

5

Addresses

Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.

Keywords

Humans, Musculoskeletal Diseases, Arthritis, Rheumatoid, Osteoarthritis, Hydroxyproline, Citrulline, Autoantibodies, Early Diagnosis, Chromatography, High Pressure Liquid, Area Under Curve, Sensitivity and Specificity, ROC Curve, Algorithms, Adult, Aged, Middle Aged, Female, Male, Tandem Mass Spectrometry, Biomarkers