Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis

Background: The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) lev el was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an impor tant inhibitor of matrix metalloproteinases (MMPs), such as interstitial co llagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However serum levels of TIMP-2 in patients with syst emic sclerosis (SSc) have not been investigated. Objective: We sought to determine the clinical significance of serum levels of TIMP-2 and MMP-2 in patients with SSc. Methods: Serum samples were obtained from 128 patients with SSc (68 with li mited cutaneous SSc and 60 with diffuse cutaneous SSc). Twenty-seven serum samples from healthy age- and sex-matched individuals were also examined as controls. The TIMP-2 and MMP-2 levels were determined by means of sandwich enzyme-linked immunosorbent assays. Results: The serum TIMP-2 levels were elevated in 29 (22.7%) of the 128 pat ients with SSc and were significantly higher than those of the healthy cont rol subjects. The serum TIMP-2 levels were significantly correlated with th e extent of skin sclerosis in the patients with SSc. The incidence of decre ased percentage of the diffusing capacity of lung for carbon monoxide (DLCO ) and that of an elevated erythrocyte sedimentation rate were significantly greater in the patients with elevated TIMP-2 levels compared with the pati ents with normal TIMP-2 levels (P < .05). When these patients were classifi ed into 2 groups by disease activity, TIMP-2 levels were significantly more elevated in the high active group than in those low active group (P < .001 ). The serum MMP-2 levels of the patients with SSc were not significantly h igher than those of the healthy control subjects. Conclusion: These findings suggest that the serum TIMP-2 level is a useful marker of the extent of skin sclerosis and disease activity in patients wit h SSc. The balance of TIMP-2 and MMP-2 may play an important role in patien ts with SSc. Furthermore, TIMP-2 may be thought to contribute to the develo pment of disease in patients with SSc.