Matrix metalloproteinases, but not cathepsins B, H, and L or their inhibitors in peripheral blood of patients with rheumatoid arthritis are potentially useful markers of disease activity
G. Keyszer et al., Matrix metalloproteinases, but not cathepsins B, H, and L or their inhibitors in peripheral blood of patients with rheumatoid arthritis are potentially useful markers of disease activity, Z RHEUMATOL, 57(6), 1998, pp. 392-398
Objective: The clinical activity of rheumatoid arthritis (RA) is not reliab
ly reflected by laboratory measures. Proteolytic enzymes involved in the ca
scade of joint destruction are potentially useful parameters to monitor the
extent of joint inflammation in RA. This study compares the validity of tw
o classes of proteolytic enzymes, matrix metalloproteinases (MMP) and lysos
omal cysteine proteinases (cathepsin B, I-I, and L) as well as their respec
tive inhibitors to serve as parameters of RA disease activity.
Methods: The proteolytic activity of cathepsins B, H, and L was determined
by fluorometry in sera of 20 patients with active RA and of 20 healthy dono
rs. In addition, the concentrations of cathepsin B and L as well as of cath
epsin inhibitors stefin A, stefin B, and cystatin C were measured by ELISA.
The plasma concentrations of MMP-1 (collagenase), MMP-3 (stromelysin), tis
sue inhibitor of metalloproteinases 1 (TIMP-1), and of MMP-1/TIMP-1 complex
(MT complex) were analyzed by ELISA as well.
Results: A significant increase of MMP-1, MMP-3, and MT complex was observe
d in RA plasma, compared to normal controls, whereas TIMP-1 concentrations
did not differ. In contrast, neither serum activity nor protein concentrati
on of any of the cathepsins or cathepsin inhibitors were elevated in RA.
Conclusion: Despite ample evidence in the literature that cathepsin activit
y contributes to the pathogenesis of inflammatory joint disease, this is no
t reflected by the conditions in peripheral blood. In contrast to the cyste
ine proteinases, MMP-1 and MMP-3 as well as MT complex are elevated in RA.
In the context of findings in the literature, this stresses the importance
of MMP as disease activity markers, compared to cysteine proteinases or the
ir inhibitors.