Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Analysis of a Broad Spectrum of Urinary and Serum Biomarkers in a Large Cohort of Patients with Early Osteoarthritis of Hip and/or Knee (CHECK): The First Results
van Spil, Willem E., Lafeber, Floris P. J. G., Jansen, Nathalie W. D.
Biomarkers to diagnose OA in an early stage and/or to predict its course would be of great value. Therefore, we selected a broad spectrum of serum and urinary biomarkers representative of cartilage, bone and synovium turnover for evaluation in CHECK (Cohort Hip & Cohort Knee). This multi-centre cohort consists of 1002 participants with pain and/or stiffness of knee and/or hip, aged 4565 yrs, and who had never or no longer than 6 months before visited their physician for these symptoms for the first time. Hip and knee radiographs as well as clinical parameters and multiple questionnaires are evaluated at regular intervals. Furthermore, serum (s) and urine (u) samples are collected at 0, 2, 5, 8, and 10 yrs. Baseline biomarker measurement has recently been completed and would provide a unique opportunity to study the diagnostic and prognostic properties of biomarkers in early-stage OA. This abstract covers quality aspects of this large biomarker set.
Baseline samples were thawed for the first time. Commercially available ELISA assays were performed to measure uCTX-II, uCTX-I (ImmunoDiagnostic Systems Ltd.), uNTX-I (Wampole Laboratories), sCOMP (Anamar Med AB), sOC (IDS), sHA (Corgenix Inc.), sPIIANP (Millipore Corp.), sCS846, and sC1,2C (IBEX) and RIA assays for sPINP and sPIIINP (Orion Diagnostica). There was no commercial involvement and kits were from the same badge for each biomarker. Each biomarker was measured in all samples by the same technician in 8 days in a period of 6 wks using 14 kits.
Quality of the assays, checked by using a randomly distributed pooled reference sample, controls as supplied by manufacturers, and blank samples in-between patient samples, was acceptable, except for the COMP assay. The COMP assay showed a remarkably variable biomarker concentration within and between assay plates.
When biomarker concentrations of all patient samples were plotted in chronological order of assaying, it appeared that there was a sufficient window of variation within a positively skewed distribution. There was no evident variation over time and between serial kits of the same assay, except for two remarkable observations: part of the sCOMP kits showed biomarker concentrations that were a 10-fold higher and showed significantly more variation than the other kits. For the sC1,2C and sCS846 assays, there was a relationship between measured biomarker concentration and sample position within assay plates. It appeared that the variation in the COMP assays was due to the coating procedure and the assay will be run again with new kits. For the C1,2C and CS846 assays there is still ongoing research to specify the problem.
Reliable measurement seems possible for the majority of the studied biomarkers in this large sample set. However, there remain some challenges for some of the assays before actual correlations with clinical and radiographic data can be made.
To cite this abstract, please use the following information:
van Spil, Willem E., Lafeber, Floris P. J. G., Jansen, Nathalie W. D.; Analysis of a Broad Spectrum of Urinary and Serum Biomarkers in a Large Cohort of Patients with Early Osteoarthritis of Hip and/or Knee (CHECK): The First Results [abstract]. Arthritis Rheum 2009;60 Suppl 10 :824