Serum matrix metalloproteinase-3 and fibrin degradation product levels correlate with clinical disease activity in rheumatoid arthritis.
OBJECTIVE
Plasmin and matrix metalloproteinase-3 (MMP-3) have been linked to articular destruction in rheumatoid arthritis (RA). We compared circulating levels of plasmin-mediated fibrin degradation product (FDP D-dimer) and MMP-3 with traditional parameters of disease activity in RA to determine their clinical utility.


METHODS
Serum levels of MMP-3 and D-dimer were determined by enzyme-linked immunoassays in 60 patients with RA. Twenty healthy females and 21 patients with systemic lupus erythematosus (SLE) served as controls.


RESULTS
MMP-3 (436.8 +/- 474.2 ng/ml) and D-dimer levels (351.2 +/- 296.3 ng/ml) were markedly elevated in the sera from RA patients as compared with healthy controls (43.9 +/- 15.2 ng/ml and 63.0 +/- 64.1 ng/ml, p < 0.0001, respectively). Both levels strongly correlated with each other (r = 0.627, p < 0.0001) and were closely associated with various clinical parameters for the disease activity of RA, including the erythrocyte sedimentation rate (ESR) and the Lansbury's activity index (p < 0.0001). MMP-3 levels were more highly correlated with articular parameters such as the swollen and painful joint counts (r = 0.454, p = 0.0002), whereas D-dimer levels correlated well with C-reactive protein (CRP) levels (r = 0.581, p < 0.0001). In SLE patients, MMP-3 (239.1 +/- 199.6 ng/ml, p < 0.0001) and D-dimer levels (86.9 +/- 85.2 ng/ml, p = 0.0278) were also higher than in healthy controls. Both levels correlated with each other (r = 0.612, p = 0.0025), and were associated with ESR and CRP levels, as was observed in RA patients, but not with most of the other clinical indicators for SLE.


CONCLUSIONS
Serum levels of MMP-3 and D-dimer are clinically useful indicators for disease activity in RA. Our results further support the hypothesis that MMP-3 and plasmin may interact in the inflammatory synovial tissues, and thus augment the articular destruction seen in RA. In SLE patients, however, MMP-3 producing cells could be different from in RA patients, and further studies will be required to clarify the pathogenetic mechanism underlying the raised serum levels of MMP-3 and/or D-dimer.
Department of Internal Medicine 4, Tokai University School of Medicine, Kanagawa, Japan.
Y
Y
Ichikawa
C
C
Yamada
T
T
Horiki
Y
Y
Hoshina
M
M
Uchiyama
D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology*; D015415:Biomarkers; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000503:physiopathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D012720:Severity of Illness Index
D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3