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. 2001 Sep;60(9):846–851.

Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls

S Young-Min 1, C Beeton 1, R Laughton 1, T Plumpton 1, S Bartram 1, G Murphy 1, C Black 1, T Cawston 1
PMCID: PMC1753839  PMID: 11502611

Abstract

BACKGROUND—Excess tissue matrix accumulates in systemic sclerosis (SSc), accounting for both visceral and dermal fibrosis. It is suggested that decreased serum levels of matrix metalloproteinases (MMPs) or increased levels of tissue inhibitors of matrix metalloproteinases (TIMPs) may account for this matrix accumulation.
OBJECTIVE—To measure serum levels of tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and collagenase-1 (MMP-1), in patients with diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), primary Raynaud's phenomenon (RP), and in normal controls.
METHODS—Serum samples from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), and normal controls (n=98) were analysed using enzyme linked immunosorbent assays (ELISAs) for total TIMP-1, TIMP-2, and MMP-1. Results from each assay were analysed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups.
RESULTS—TIMP-1 levels were significantly raised in dcSSc and lcSSc groups compared with the RP group and normal controls (p<0.01 to p<0.001). In the dcSSc group, TIMP-1 levels were significantly higher in early disease (<2 years) than in late stage disease (>4 years) (p<0.05). This was not found for the lcSSc group. Serum TIMP-2 and MMP-1 levels in dcSSc and lcSSc did not differ significantly from those in normal controls. Increased levels of TIMPs were not convincingly associated with organ disease. No assay result correlated with autoantibody status (anti-topoisomerase 1 (anti-Scl-70), anticentromere antibody, or anti-RNA polymerase). No significant differences in serum TIMP-1, TIMP-2, or MMP-1 levels were shown in the RP group compared with normal controls.
CONCLUSIONS—Raised TIMP-1 levels in the SSc groups support the hypothesis that matrix accumulation occurs in SSc at least in part owing to decreased degradation. Moreover, the variation in TIMP-1 levels between the early and late disease stages of dcSSc seems to reflect the early progressive course of dermal fibrosis seen clinically. The expected reduction in serum MMP-1 levels in the SSc groups was not found. This suggests that tissue matrix accumulation is due to increased inhibitors rather than to decreased MMPs.



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Figure 1  .

Figure 1  

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Serum TIMP-1 level in diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), Raynaud's phenomenon (RP), and normal groups. Box plots with upper and lower bars showing the data range, and upper, middle, and lower lines in the box showing 75th, 50th (median), and 25th centiles respectively. Kruskal-Wallis test across all four groups p<0.0001. Only significant Dunn's multiple comparison post-test p values between groups shown.

Figure 2  .

Figure 2  

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Serum TIMP-2 level in diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), Raynaud's phenomenon (RP), and normal groups. Box plots with upper and lower bars showing the data range, and upper, middle, and lower lines in the box showing 75th, 50th (median), and 25th centiles respectively. Kruskal-Wallis test across all four groups p<0.0001. Only significant Dunn's multiple comparison post-test p values between groups shown.

Figure 3  .

Figure 3  

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Serum MMP-1 level in diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), Raynaud's phenomenon (RP), and normal groups. Box plots with upper and lower bars showing the data range, and upper, middle, and lower lines in the box showing 75th, 50th (median), and 25th centiles respectively. Kruskal-Wallis test across all four groups p=0.001. Only significant Dunn's multiple comparison post-test p values between groups shown.

Figure 4  .

Figure 4  

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Serum TIMP-1 level in diffuse cutaneous systemic sclerosis (dcSSc)—reduction in level at different disease stages. Box plots with upper and lower bars showing the data range, and upper, middle, and lower lines in the box showing 75th, 50th (median), and 25th centiles respectively. Kruskal-Wallis test across all three groups p=0.02. Dunn's multiple comparison post-test between early and late stages p<0.05.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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