Different cartilage oligomeric matrix protein (COMP) patterns in untreated anti-CCP positive and negative rheumatoid arthritis (RA)

Purpose: COMP is an extracellular matrix protein, which is primarily localized in cartilage. The protein is believed to regulate collagen fibril formation and matrix assembly. In RA and osteoarthritis there is an altered distribution of COMP in cartilage and COMP release to synovial fluid is increased. The aims were to measure COMP in serum and paired synovial fluid samples in early, untreated RA and to study the predictive value of baseline COMP on structural joint damage at 5 years. Method: One-hundred-and-sixty patients with DMARD naïve and newly-diagnosed RA were included in the CIMESTRA trial [1]. 90 blood donors served as controls. Disease activity measures (e.g. CRP), x-ray (n=160) and magnetic resonance imaging (MRI) of non-dominant wrist (n=135) were obtained at baseline. In addition, x-ray status was obtained at 5 years. Radiographic progression was defined as the minimal detectable difference from baseline using Sharp/van der Heijde Score. MRI synovitis, oedema and erosion score were assessed according to OMERACT criteria. Anti-CCP was assayed at baseline. COMP was measured in serum and synovial fluids at baseline by ELISA (AnaMar, Sweden). Synovial fluids were collected from 22 patients at baseline. Results: COMP was increased in RA serum as compared with controls (p<0.001). However, anti-CCP positive patients had significantly lower COMP than anti-CCP negative subjects (p=0.048), although still elevated compared with controls (p=0.042). In both subsets COMP correlated with DAS28 and joint counts. In anti-CCP positive patients COMP was positively correlated to MRI erosion and oedema score (rho=0.37, p<0.001 and rho=0.26, p=0.02). In anti-CCP negatives there was a positive correlation between COMP and MRI synovitis score (rho=0.32, p=0.02). Baseline COMP did not predict x-ray progression at 5 years. Synovial fluid COMP was 3.8 times higher than COMP in serum, but did not correlate to serum values (p=0.95). Conclusion: COMP is increased in early DMARD naïve RA. Anti-CCP negative patients had higher COMP in serum than anti-CCP positives. These findings indicate that anti-CCP antibodies are disease modifiers in RA as also reflected by the differential association of COMP with erosion and synovitis score at baseline in these two subsets.