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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:
  • 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.



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.


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.


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.


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.


ARGS; Aggrecan; Biomarker; Immunoassay; Neoepitope; Osteoarthritis

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