Deberg Michelle, Labasse Alain, Christgau Stephan, Cloos Paul, Bang Henriksen Dennis, Chapelle Jean-Pierre, Zegels Brigitte, Reginster Jean-Yves, Henrotin Yves
Bone and Cartilage Research Unit, University of Liège, Sart Tilman, 4000 Liège, Belgium.
Osteoarthritis Cartilage. 2005 Mar;13(3):258-65. doi: 10.1016/j.joca.2004.12.002.
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.
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).
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.
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.
蛋白质硝化是关节炎症过程的一个显著特征。我们已开发出针对生物体液中II型胶原蛋白α螺旋区域的肽段108HRGYPGLDG116（Coll 2-1）及其硝化形式108HRGY(NO2)PGLDG116（Coll 2-1 NO2）的特异性免疫测定方法。
将Coll 2-1和Coll 2-1 NO2肽段注射到兔子体内。选择了两种具有特异性和亲和力的抗血清（D3和D37），并用于开发特异性免疫测定方法。在242名健康受试者（N）、67名原发性膝关节骨关节炎（OA）患者和19名类风湿关节炎（RA）患者的血清中检测Coll 2-1和Coll 2-1 NO2。
在健康受试者中，Coll 2-1和Coll 2-1 NO2的浓度分别为125.13±3.71 nM和0.16±0.08 nM。在OA和RA患者中，与相同年龄范围的对照组相比，Coll 2-1和Coll 2-1 NO2的血清水平显著升高（Coll 2-1：OA：200.80±8.98 nM，RA：172.30±19.05 nM, 正常：126.60±6.70 nM；Coll 2-1 NO2：OA：0.26±0.02，RA：0.38±0.05，正常：0.12±0.01 nM）。RA患者中Coll 2-1 NO2水平的升高显著高于OA患者（P<0.05）。因此，RA患者中Coll 2-1 NO2/Coll 2-1的比值比OA患者高1.6倍。未发现放射学OA严重程度与血清中Coll 2-1和Coll 2-1 NO2水平之间存在相关性。在OA和RA患者的血清中，Coll 2-1 NO2与C反应蛋白相关，但Coll 2-1与C反应蛋白无关。
测定关节炎患者血清中的Coll 2-1和Coll 2-1 NO2似乎是检测氧化相关软骨降解事件的一种有前景的有用工具。此外，这些标志物有助于监测抗炎或抗氧化药物对软骨降解的影响。
