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.
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.


METHODS
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.
Deberg
Michelle
M
Bone and Cartilage Research Unit, University of Liège, Sart Tilman, 4000 Liège, Belgium.
Labasse
Alain
A
Christgau
Stephan
S
Cloos
Paul
P
Bang Henriksen
Dennis
D
Chapelle
Jean-Pierre
JP
Zegels
Brigitte
B
Reginster
Jean-Yves
JY
Henrotin
Yves
Y
D000328:Adult; D000375:Aging / Q000097:blood; D000818:Animals; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D024043:Collagen Type II / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005609:Free Radicals / Q000097:blood; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D010003:Osteoarthritis / Q000097:blood* / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000097:blood; D011817:Rabbits; D015203:Reproducibility of Results
D015415:Biomarkers; D024043:Collagen Type II; D005609:Free Radicals; D007106:Immune Sera; D009566:Nitrates; D010446:Peptide Fragments