RT Journal Article SR Electronic T1 Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 1094 OP 1099 DO 10.1136/ard.62.11.1094 VO 62 IS 11 A1 I Tchetverikov A1 L R Lard A1 J DeGroot A1 N Verzijl A1 J M TeKoppele A1 F C Breedveld A1 T W J Huizinga A1 R Hanemaaijer YR 2003 UL http://ard.bmj.com/content/62/11/1094.abstract AB 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.