Serum Tissue Inhibitor of Metalloproteinases in Patients with Systemic Sclerosis

Background: One of the suggested contributory factors to the development of dermal fibrosis is a decrease in collagenase activity, which may be related to levels of serum tissue inhibitors of metalloproteinase-1 (TIMP-1).

Objective: The aim of this study was to determine the clinical significance of serum TIMP-1 levels in systemic sclerosis (SSc).

Methods: We measured serum TIMP-1 concentration in 62 patients with SSc, 11 patients with systemic lupus erythematosus, 14 patients with rheumatoid arthritis, and 22 members of a normal control group. The clinical features of the patients with SSc and elevated TIMP levels were examined.

Results: The mean TIMP-1 level in the patients with SSc was significantly higher than that in the members of the control group or the patients with systemic lupus erythematosus or rheumatoid arthritis. In 44% of the patients with SSc the serum TIMP-1 level was elevated. The mean serum TIMP-1 level in patients with diffuse cutaneous SSc (dSSc) was significantly higher than that in those with limited cutaneous SSc. The patients with dSSc and elevated serum TIMP-1 levels showed a significantly greater incidence of lung fibrosis and anti-topoisomerase I antibody than those with normal serum TIMP-1 levels. The TIMP-1 level and diffusing capacity for carbon monoxide in the patients with SSc were negatively correlated. Increased mitogenic activity on dermal fibroblasts caused by serum from patients with dSSc was partially blocked by anti-TIMP-1 IgG.

Conclusions: These findings suggest that serum TIMP-1 level is a useful indicator of disease activity in patients with SSc and that TIMP is involved in the pathogenesis of SSc.