Serum and synovial fluid concentrations of matrix metalloproteinases 3 and its tissue inhibitor 1 in juvenile idiopathic arthritides.
OBJECTIVE
Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption in idiopathic arthritides. We investigated serum and synovial fluid (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile idiopathic arthritides (JIA).


METHODS
Sera from 45 patients with active, 15 patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA.


RESULTS
MMP-3 serum concentrations were significantly higher in patients with active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p = 0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but not TIMP-1, concentration displayed a variable degree of correlation with clinical and laboratory variables of disease activity and with p75 sTNFR concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02-1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p < 0.001).


CONCLUSIONS
MMP-3 (stromelysin-1) is clearly overexpressed in SF of patients with JIA. An inadequate counter-expression of TIMP-1 may represent a crucial event for the development and perpetuation of tissue damage.
Gattorno
Marco
M
2nd Division of Pediatrics, G. Gaslini Institute for Children, Genoa, Italy. marcogattorno@ospedale-gaslini.ge.it
Vignola
Silvia
S
Falcini
Fernanda
F
Sabatini
Federica
F
Buoncompagni
Antonella
A
Simonini
Gabriele
G
Picco
Paolo
P
Pistoia
Vito
V
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3