Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Novel Serum Biomarker of Cartilage Destruction, Measured in OA and RA Patients, Is Significantly Associated with Kellgren-Lawrence Score.
Bay-Jensen1, Anne C., Dam3, Erik B., Byrjalsen2, Inger, Schubert4, Tanja, Vergnaud4, Phillip, Qvist1, Per, Karsdal1, Morten A.
Type II collagen is the primary matrix protein in articular cartilage. In joint degenerative diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA), the collagens are degraded by matrix metalloproteinases (MMPs) and fragments of the protein are released into the circulation. We identified one such fragment of MMP-derived type II collagen (CIIM).
Type II collagen was cleaved with MMP in vitro and analyzed by mass spectrometry. A collagen type II specific neoepitope, CIIM, was identified (RDGAAG1053). Monoclonal antibodies were raised against the neoepitope and used to develop an ELISA. CIIM assay was measured in the synovial fluid of 18 OA patients aged 6281 and in serum of an adult population aged 2180 (n=156). Knee OA was graded by standard Kellgren-Lawrence (KL) score. Serum levels was measured in serum samples from RA patients and age-matched controls (n=66).
The CIIM ELISA showed good technical performance; a quantification range of 0.214.9ng/ml, inter- and intra assay variations below <15% and a dilution recovery of approximately 100%. CIIM was immunolocalized to classical arthritis features in OA cartilage. A high median level of CIIM [1.2ng/ml] was found in synovial fluid. Serum CIIM levels were significantly higher (p<0.05) in those individuals with OA detected by KL scores of 12 [0.9ng/ml] and 34 [1.0ng/ml] than in those with KL score of 0 [0.6ng/ml] (Fig. 1). The level of CIIM in RA serum [0.284ng/ml] was significantly higher (p<0.01) than age-matched controls [0.532ng/ml].
We developed and validated an ELISA for CIIM; a novel biomarker which we demonstrated is derived from MMP-degraded type II collagen. We found serum CIIM levels to be highest in those with the lowest KL score and with RA.
To cite this abstract, please use the following information:
Bay-Jensen, Anne C., Dam, Erik B., Byrjalsen, Inger, Schubert, Tanja, Vergnaud, Phillip, Qvist, Per, et al; A Novel Serum Biomarker of Cartilage Destruction, Measured in OA and RA Patients, Is Significantly Associated with Kellgren-Lawrence Score. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1466