The association of serum matrix metalloproteinases and their tissue inhibitor levels with scleroderma disease severity

Abstract

Objective. Matrix metalloproteinase 3 (MMP-3) is reported to play an important role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Studies have also investigated the association of different tissue inhibitors of MMPs (TIMPs) with fibrosis in scleroderma (SSc). The aim of this study was to evaluate the correlation of serum MMP-1, 3 and TIMP-1 with severity and disease specific markers of SSc and RA. Methods. Serum MMP-1,3 and TIMP-1 were measured in 42 SSc patients (age range 28-68 yr, mean 47 yr) and compared to 29 RA and 30 healthy age-and sex-matched individuals. Elevated values of MMPs and TIMP-1 were defined as those greater than 2 SD above the normal mean. All SSc and RA patients were scored for disease severity. Results. Serum MMP-1 was significantly elevated in 8/42 (19%) SSc patients (p = 0.01) but only in 2/29 (7%) RA patients (p = 0.2). Whereas MMP-3 levels were elevated in 10/29 (34%) RA patients (p = 0.002), it was elevated in only 5/42 (12%) SSc patients (p = 0.03). TIMP-1 was found elevated in 17/42 (40%) SSc patients (p = 0.001) and in only 4/29 RA patients (with a strong trend towards significance, p = 0.052). We found a significant association between the elevation of both MMPs and TIMP-1 levels, with the severity of SSc. Those who had an increase of more than one MMP and/or TIMP, demonstrated life-threatening major organ involvement such as end stage lung fibrosis, GI aperislasis, and severe cardiac failure. Contrary to that in SSc, the severity of RA showed some trend of association with MMP-3 only. Conclusion. We confirm previous observations that MMPs and TIMPs may play an important role in various rheumatic diseases. Whereas serum increase of MMP-3 correlated with RA severity, SSc severity was more characterized by the increase of both MMP-1 and TIMP-1. This suggests that the MMPs and TIMPs involved in SSc are different than those playing a role in RA, which may indicate that in SSc they are produced in different locations than in RA.