Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis.

Abstract

OBJECTIVE:

To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in alpha(2) macroglobulin (alpha(2)M)/MMP complexes and the progression of joint destruction in patients with recent onset rheumatoid arthritis (RA).

METHODS:

109 patients with RA of recent onset were entered into this longitudinal study. Patients were followed up for two years; clinical data, blood samples, and radiographs were obtained at baseline and at 1 and 2 years. Serum levels of MMPs were measured by sandwich ELISA and MMP activity assays.

RESULTS:

During the two years joint damage progressed from 0 to 10 (median Sharp score, p<0.001). Stable levels of pro-MMP-3 and a significant decrease in the levels of pro-MMP-8 and -9 and alpha(2)M/MMP complexes were seen throughout the two years. Regression analysis showed that serum pro-MMP-3 levels at disease onset were independently associated with the progression of joint damage (B=0.7, 95% CI 0.3 to 1.1, p=0.001). Based on the rate of joint destruction, patients were divided into two subgroups: patients with mild and severe joint damage progression. The pro-MMP-3 levels were significantly higher in the group with severe compared with mild disease at all times. Levels of pro-MMP-8 and -9 were decreased in both groups, whereas alpha(2)M/MMP complex levels decreased in the group with mild disease only.

CONCLUSION:

Serum levels of the MMPs studied are associated with disease activity, but serum pro-MMP-3 levels at the onset of disease are also predictive of joint damage progression.

• Authors: I Tchetverikov, L R Lard, J DeGroot, N Verzijl, J M TeKoppele, F C Breedveld, T W J Huizinga, R Hanemaaijer
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 62 Issue 11 Pg. 1094-9 (Nov 2003) ISSN: 0003-4967 [Print] England
• PMID: 14583574 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• alpha-Macroglobulins
• C-Reactive Protein
• Matrix Metalloproteinases
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 9

Topics

• Adult
• Arthritis, Rheumatoid (blood, pathology)
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• Disease Progression
• Female
• Humans
• Joints (pathology)
• Male
• Matrix Metalloproteinase 3 (blood)
• Matrix Metalloproteinase 9 (blood)
• Matrix Metalloproteinases (blood)
• Middle Aged
• Prospective Studies
• Statistics, Nonparametric
• alpha-Macroglobulins (metabolism)