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: Usman Ahmed, Attia Anwar, Richard S Savage, Matthew L Costa, Nicola Mackay, Andrew Filer, Karim Raza, Richard A Watts, Paul G Winyard, Joanna Tarr, Richard C Haigh, Paul J Thornalley, Naila Rabbani
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 9259 (Mar 19 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25788417 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Biomarkers
• Citrulline
• Hydroxyproline

Topics

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