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

Background: The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) level was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an important inhibitor of matrix metalloproteinases (MMPs), such as interstitial collagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However serum levels of TIMP-2 in patients with systemic 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 limited 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 patients with SSc and were significantly higher than those of the healthy control subjects. The serum TIMP-2 levels were significantly correlated with the extent of skin sclerosis in the patients with SSc. The incidence of decreased 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 patients with normal TIMP-2 levels (P < .05). When these patients were classified 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 higher 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 with SSc. The balance of TIMP-2 and MMP-2 may play an important role in patients with SSc. Furthermore, TIMP-2 may be thought to contribute to the development of disease in patients with SSc.