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New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis.

Deberg M, Labasse A, Christgau S, Cloos P, Bang Henriksen D, Chapelle JP, Zegels B, Reginster JY, Henrotin Y

Bone and Cartilage Research Unit, University of Liège, Sart Tilman, 4000 Liège, Belgium.

OBJECTIVE: Protein nitration is a prominent feature of inflammatory processes in the joint. We have developed immunoassays specific for a peptide of the alpha-helical region of type II collagen 108HRGYPGLDG116 (Coll 2-1) and its nitrated form 108HRGY(NO2)PGLDG116 (Coll 2-1 NO2) in biological fluids. DESIGN: Coll 2-1 and Coll 2-1 NO2 peptides were injected into rabbits. Two antisera (D3 and D37) were selected for their specificity and affinity and used to develop specific immunoassays. Coll 2-1 and Coll 2-1 NO2 were measured in sera of 242 healthy subjects (N), 67 patients with primary knee osteoarthritis (OA) and 19 patients with rheumatoid arthritis (RA). RESULTS: In healthy subjects, Coll 2-1 and Coll 2-1 NO2 concentrations were 125.13+/-3.71 nM and 0.16+/-0.08 nM, respectively. In OA and RA, Coll 2-1 and Coll 2-1 NO2 serum levels were found to be significantly increased compared to controls of the same range of age (Coll 2-1: OA: 200.80+/-8.98 nM, RA: 172.30+/-19.05 nM, normal: 126.60+/-6.70 nM and Coll 2-1 NO2: OA: 0.26+/-0.02, RA: 0.38+/-0.05, normal: 0.12+/-0.01 nM). Coll 2-1 NO2 levels were significantly more elevated in RA than in OA patients (P<0.05). As a consequence, the ratio Coll 2-1 NO2/Coll 2-1 was 1.6 times higher in RA than in OA subjects. No relationship was found between the radiological OA severity and the levels of Coll 2-1 and Coll 2-1 NO2 in serum. Coll 2-1 NO2, but not Coll 2-1, was correlated with C-reactive protein in the sera of OA and RA patients. CONCLUSIONS: The determination of both Coll 2-1 and Coll 2-1 NO2 in serum of arthritic patients seems to be a promising useful tool for the detection of oxidative-related cartilage degradation episode. Further, these markers could be helpful for monitoring the effects of anti-inflammatory or antioxidant drugs on cartilage degradation.

Published 24 February 2005 in Osteoarthritis Cartilage, 13(3): 258-65.
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