Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers

Objective. To investigate whether plasma levels of matrix metalloproteinase s 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metallop roteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex (MT complex) are specifical ly elevated in erosive joint diseases compared to nonerosive rheumatic dise ases, and to assess how these markers reflect the clinical activity of rheu matoid arthritis (RA) compared to circulating cytokines and markers of conn ective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. Methods. Plasma levels of MMP-3, MMP-1, TIMP-1, and MT complex were determi ned by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS ), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating in flammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TN F-alpha), and IL-6], collagen degradation products, and markers of bone for mation were determined in parallel and were correlated to 4 variables of cl inical activity. Results. MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupu s erythematosus (SLE), MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, TWT complex was elevated in RA only. TIMP-1 was not different from controls. C RP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak co rrelation of IL-6 with clinical measures. Among variables of connective tis sue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakl y correlated with disease activity. Conclusion. Elevated MMP-3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-I with cl inical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CR P with clinical activity.