Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis. Issue 11 (28th October 2003)

• Record Type: Journal Article
• Authors: Tchetverikov, I; Lard, L R; DeGroot, J; Verzijl, N; TeKoppele, J M; Breedveld, F C; Huizinga, T W J; Hanemaaijer, R
• Is Part Of: Annals of the rheumatic diseases. Volume 62:Issue 11(2003)
• Page Start: 1094
• Page End: 1099
• Publication Date: 2003-10-28
• Subjects: matrix metalloproteinases -- rheumatoid arthritis -- joint damage; 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; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.62.11.1094
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in α2 macroglobulin (α2 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 α2 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 α2 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.