Format

Send to:

Choose Destination
See comment in PubMed Commons below
Osteoarthritis Cartilage. 2014 May;22(5):690-7. doi: 10.1016/j.joca.2014.02.930. Epub 2014 Feb 28.

Quantitation OF ARGS aggrecan fragments in synovial fluid, serum and urine from osteoarthritis patients.

Author information

  • 1GlaxoSmithKline Biopharmaceutical Research & Development, Stevenage, Herts, UK. Electronic address: fiona.m.germaschewski@gsk.com.
  • 2GlaxoSmithKline Research & Development, King of Prussia, PA, USA.
  • 3GlaxoSmithKline Biopharmaceutical Research & Development, Stevenage, Herts, UK.
  • 4Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK.
  • 5GlaxoSmithKline Clinical Unit, Addenbrookes, Cambridge, UK.

Abstract

OBJECTIVE:

To characterise ARGS neoepitope concentrations in various matrices from patients with knee osteoarthritis (OA) and assess performance of an immunoassay to facilitate clinical development of therapeutics affecting the A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) pathway.

DESIGN:

Matched sera, urine, and synovial fluid (SF) (surgical subjects only) were collected from healthy subjects, subjects with knee OA (non-surgical OA), and OA subjects undergoing total knee replacement (OA-TKR; n = 20 per group). Diurnal and inter-day variation was evaluated in the non-surgical OA group over 3 separate visits. Serum and urine samples were collected on two visits for the OA-TKR group with SF taken only at the time of surgery. ARGS neoepitope was quantitated using an optimized immunoassay.

RESULTS:

Serum ARGS neoepitope concentrations were elevated in OA-TKR subjects compared to non-surgical OA subjects (P = 0.005) and healthy subjects (P = 0.0002). Creatinine corrected urinary ARGS neoepitope concentrations were more variable, but were also elevated in the OA-TKR subjects compared to healthy subjects (P = 0.008). No significant diurnal effect or inter-day variance was observed in serum or urine. Serum ARGS neoepitope concentrations correlated with age (P = 0.0252) but not with total number of joints with OA involvement. SF ARGS neoepitope concentrations correlated with Western Ontario and MacMaster OA Index (WOMAC) stiffness score (P = 0.04) whereas a weaker, non-significant trend towards positive correlation with combined WOMAC score and the number of concurrent joints was observed.

CONCLUSIONS:

This study utilized a sensitive and robust assay to evaluate ARGS neoepitope concentrations in various matrices in OA patients and healthy volunteers. ARGS neoepitope appears promising as a prognostic/stratification marker to facilitate patient selection and as an early pharmacodynamic marker for OA therapeutic trials.

Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

ARGS; Aggrecan; Biomarker; Immunoassay; Neoepitope; Osteoarthritis

PMID:
24583346
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk