Characteristics of the protease activity in synovial fluid from patients with rheumatoid arthritis and osteoarthritis

Objective To clarify which proteases are specifically activated in the lesions of rhe umatoid arthritis (Ra) and osteoarthritis (OA). Methods The activity levels of the serine proteases of the coagulation and fibrinol ytic systems, and of elastase and collagenase as controls, in synovial flui d from 27 RA patients and 28 OA patients were measured using fluorogenic sy nthetic substrates which had methylcoumarylamide (MCA) at their COOH-termin i. The thrombin-antithrombin III complex (TAT) content was also measured by ELISA. Results Among the proteases, thrombin-like activity was the highest in both RA and OA. The profiles of protease activity were similar in RA and OA, but their activities were in general significantly higher in RA than in OA (p < 0.01) . The levels of both thrombin-like activity and TAT were about 7.5-fold hig her in RA than in OA, while the levels of CRP and fibrinogen were only abou t 2-fold higher Biochemical characterization of the thrombin-like activity in the synovial fluid of RA patients showed that this activity was due to t hrombin. Thrombin-like activity positively correlated with the TAT concentr ation in RA (r = 0.750 p < 0.0001) but not in OA. Conclusion Activation of the coagulation system was more marked in RA than in OA, stro ngly suggesting that in RA there is an imbalance between thrombin and its i nhibitors, and that thrombin is more closely linked to the pathogenesis of RA than to that of OA. Our results also show that analysis of the synovial fluid may be useful to estimate the activation of the coagulation system in RA, but not that of the fibrinolytic system.