Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis
- I Tchetverikov1,2,
- L R Lard2,
- J DeGroot1,
- N Verzijl1,
- J M TeKoppele1,
- F C Breedveld2,
- T W J Huizinga2,
- R Hanemaaijer1
- 1TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
- 2Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
- Correspondence to:
Dr R Hanemaaijer, TNO Prevention and Health, PO Box 2215, 2301 CE, Leiden, The Netherlands;
- Accepted 28 April 2003
Objective: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in α2 macroglobulin (α2M)/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 α2M/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 α2M/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.
- ACR, American College of Rheumatology
- α2M, α2 macroglobulin
- CI, confidence interval
- CRP, C reactive protein
- DAS, disease activity score
- DMARD, disease modifying antirheumatic drug
- EAC, early arthritis clinic
- ELISA, enzyme linked immunosorbent assay
- JDS, joint damage score
- MMP, matrix metalloproteinase
- RA, rheumatoid arthritis
- RF, rheumatoid factor
- SE, shared epitope
- SF, synovial fluid
- TIMP, tissue inhibitor of matrix metalloproteinase