Tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-3 in Japanese healthy children and in Kawasaki disease and their clinical usefulness in juvenile rheumatoid arthritis

BACKGROUND AND METHODS: To determine the clinical values of tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase-3 (MMP-3) in juvenile rheumatoid arthritis (JRA), we measured serum levels of these enzymes with rapid one-step sandwich enzyme immunoassay. Forty-one JRA patients, 48 normal healthy children (NC) and 10 Kawasaki disease (KD) patients were investigated. RESULTS: Serum TIMP-1 levels in NC corresponded to those in normal adults reported in the literature, while MMP-3 levels were lower than those in healthy children and the ratio of MMP-3/TIMP-1 decreased. The TIMP-1 levels in JRA and KD at the first clinic examination were statistically higher than those in NC (P < 0.05) and MMP-3 levels and MMP-3/TIMP-1 in JRA were significantly higher than those in NC (P < 0.0001 and 0.0005, respectively) and KD (P < 0.001 and 0.0005, respectively). In JRA, MMP-3 levels of patients with arthritis were statistically higher than those of patients without arthritis (P < 0.05) and MMP-3 levels were correlated with C-reactive protein (rs = 0.465, P < 0.05), while TIMP-1 did not (rs = 0.340). There was a positive correlation between serum levels of MMP-3 and TIMP-1 and prognosis (rs = 0.733, P < 0.05). CONCLUSION: In JRA, the serum MMP-3 level is a useful marker to evaluate joint damage, while serum TIMP-1 remains an acute phase reactant.