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THU0032 The association of serum matrix metalloproteinases and their tissue inhibitor levels with scleroderma disease severity
  1. A Kessel,
  2. E Toubi,
  3. G Grushko,
  4. E Sabo,
  5. M Rozenbaum,
  6. I Rosner
  1. Division of Clinical Immunology and Rheumatology, Bnai-Zion Medical Center, Faculty of Medicine Technion, Haifa, Israel

Abstract

Background 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).

Objectives 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 y, mean 47 y) and compared to measurement in 29 RA and healthy age/sex individuals. Elevated values of MMPs and TIMP-1 were defined as those greater than 2 S. D above 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 (0.03). TIMP-1 was found elevated in 17/42 (40%) SSc patients (p = 0.001) and in only 4/29 RA patients (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 severe lung fibrosis, diffuse GI, or kidney involvement and severe cardiac failure. Contrary to that in SSc, the severity of RA was associated 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 characterised mainly 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. These factors may play a synergistic role in the severity ofsystemic sclerosis.

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