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


CONCLUSIONS
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.
TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands.
I
I
Tchetverikov
L R
LR
Lard
J
J
DeGroot
N
N
Verzijl
J M
JM
TeKoppele
F C
FC
Breedveld
T W J
TW
Huizinga
R
R
Hanemaaijer
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D000511:alpha-Macroglobulins / Q000378:metabolism
D015415:Biomarkers; D000511:alpha-Macroglobulins; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9