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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2002 Feb;61(2):161–166. doi: 10.1136/ard.61.2.161

Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment

C Ribbens 1, y Martin 1, N Franchimont 1, M Kaiser 1, J Jaspar 1, P Damas 1, F Houssiau 1, M Malaise 1
PMCID: PMC1753989  PMID: 11796404

Abstract

Objective: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels.

Methods: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls.

Results: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups.

Conclusions: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis—that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation.

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Figure 1 .

Figure 1

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MMP-3 serum levels in female patients with various systemic diseases treated or not with corticosteroids. The horizontal line represents the median level of each group. The dotted line represents the upper normal limit of female healthy controls—that is, 14 ng/ml. Patients treated with steroids and those not treated were compared by the Mann-Whitney U test.

Figure 2 .

Figure 2

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MMP-3 serum levels in female patients with active or inactive RA not treated with steroids. The horizontal line represents the median level. The dotted line represents the upper normal limit of female healthy controls—that is, 14 ng/ml. The two groups were compared by the Mann-Whitney U test.

Figure 3 .

Figure 3

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(A) MMP-3 serum levels in nine patients with an active lupus nephritis at the time of the renal biopsy (month 0) and after three months' treatment. Steroids were started in three patients (grey symbols, dotted line) or increased in six patients treated at baseline with low dose prednisolone (black symbols, continuous line, mean dose 4.4 mg/day). The prednisolone dose was significantly higher at three months (mean dose 17.8 mg/day). Paired samples of MMP-3 and of prednisolone were compared using the Wilcoxon rank sum test. (B) Positive linear correlation between MMP-3 levels and mean prednisolone dose in the nine lupus patients at baseline (white symbols) and at month 3 (black symbols).

Figure 4 .

Figure 4

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Positive linear correlation between MMP-3 and CRP serum levels in non-steroid treated female and male patients with active (n=39) or inactive (n=7) rheumatoid arthritis.

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