Increased levels of stromelysin-1 and tissue inhibitor of metalloproteinases-1 in sera from patients with rheumatoid arthritis.
OBJECTIVE
To evaluate the efficacy of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in serum as markers for joint inflammation in rheumatoid arthritis (RA).


METHODS
Levels of both macromolecules in sera from 97 healthy controls, 109 patients with RA, and 47 patients with osteoarthritis (OA) were measured by respective 1-step sandwich enzyme immunoassays. In the patients with RA, serum levels of MMP-3 and TIMP-1 were investigated in relation to laboratory and clinical measures of disease activity. In addition, the relationships between serum and synovial fluid (SF) levels in paired samples from individual patients were examined.


RESULTS
Serum levels of both MMP-3 and TIMP-1 in RA patients were significantly higher than those in OA patients and in healthy controls (P < 0.001), and were shown to correlate with traditional systemic markers of inflammation including the erythrocyte sedimentation rate and C-reactive protein level, and with the Lansbury articular index. In addition, it was noted that serum levels of MMP-3 correlated with the corresponding values in paired SF samples obtained concurrently from patients with RA (rs = 0.588, P < 0.001), while such correlations were not found for TIMP-1 levels.


CONCLUSIONS
Our results support the notion that levels of both MMP-3 and TIMP-1 in RA patient sera are increased in association with inflammation. Furthermore, the level of MMP-3 in serum provides a particularly useful marker of inflammatory activity in the joints of patients with RA.
Yoshihara
Y
Y
National Defense Medical College, Tokorozawa, Japan.
Obata
K
K
Fujimoto
N
N
Yamashita
K
K
Hayakawa
T
T
Shimmei
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000097:blood* / Q000592:standards; D006801:Humans; D007124:Immunoenzyme Techniques; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000032:analysis / Q000097:blood* / Q000592:standards; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D013582:Synovial Fluid / Q000737:chemistry; D019714:Tissue Inhibitor of Metalloproteinases
D015415:Biomarkers; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D002097:C-Reactive Protein; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3