Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation.
OBJECTIVE
To measure serum levels of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of MMP-1 (TIMP-1) in patients with rheumatoid arthritis (RA) and in age-matched control subjects, and to determine how these correlate with serum levels of antigenic keratan sulfate (KS) and other biochemical and clinical indicators of disease activity.


METHODS
Immunoassays were used to measure levels of MMP-1, MMP-3, TIMP-1, and antigenic KS. Radiologic and functional joint scores were based upon Steinbrocker's criteria. Erythrocyte sedimentation rates (ESR) and levels of C-reactive proteins (CRP) were measured.


RESULTS
In RA patients, levels of MMP-3 and TIMP-1 were significantly increased, and strongly correlated with the ESR and CRP levels but not with radiologic or functional joint scores. Levels of antigenic KS were significantly lower in RA patients and correlated negatively with systemic parameters of inflammation and serum levels of TIMP-1.


CONCLUSIONS
The increase in serum levels of MMP-3 and TIMP-1 appears to reflect systemic inflammation in RA. The inverse correlation between serum levels of TIMP-1 and antigenic KS suggests that an upregulation of TIMP-1 synthesis might be responsible for the apparent suppression of cartilage aggrecan catabolism in patients with severe inflammatory changes.
Manicourt
D H
DH
Saint Luc University Hospital, University of Louvain, Brussels, Belgium.
Fujimoto
N
N
Obata
K
K
Thonar
E J
EJ
D000328:Adult; D000368:Aged; D000941:Antigens / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000201:enzymology / Q000276:immunology; D001175:Arthrography; D015415:Biomarkers; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D017364:Collagenases / Q000097:blood; D004906:Erythrocyte Count; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007632:Keratan Sulfate / Q000097:blood / Q000276:immunology; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D011480:Protease Inhibitors / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases
D000941:Antigens; D015415:Biomarkers; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D002097:C-Reactive Protein; D007632:Keratan Sulfate; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1