Serum activity of joint destruction proteinases in management of juvenile rheumatoid arthritis

Background

At the onset of juvenile rheumatoid arthritis (JRA), its common features including joint damage and cartilage destruction are absent. Therefore the onset of JRA is often assessed as an event of arthritis associated with infections (AAI), which precludes an early initiation of aggressive treatment with disease-modifying antirheumatic drugs to have an impact on the formation of joint destruction mediated by cathepsins and matrix metalloproteinases (MMPs).

Objectives

To determine the differences in serum activity of joint destruction enzymes between different types of inflammatory arthritis for differential diagnosis and management of JRA.

Methods

The activity of some kinds of cathepsins (B and L) by the Barrett and Kirschke method, using L-Arg-Arg-MCA and L-Phe-Arg-MCA as substrates and CA-074 as a selective inhibitor of cathepsin B, and the general activity of MMPs by the method of Nagase, using MCA-Pro-Leu-Gly-DPA-Ala-Arg-NH₂ as substrate, was measured in serum of 45 established JRA cases including relapses of disease compared with 23 AAI cases, two cases of lupus-associated arthritis, two cases of arthritis associated with ankylosing spondilitis, and 10 healthy children.

Results

On admittance to the hospital, all investigated enzyme serum activity was higher in the group of children with JRA compared with the healthy controls (P < 0.001) and the AAI group (P > 0.05) and had no differences from cases of lupus-associated arthritis and of arthritis associated with ankylosing spondilitis. But in advanced JRA cases with marked proliferative changes in the joint tissues, the initial enzyme activity was lower and increased under the treatment (P < 0.001 for cathepsin L, P > 0.05 for MMP).

Conclusion

Determining the activity of joint destructive proteinases in serum could be useful for differential diagnosis between JRA and AAI cases. Unreliable differences between these groups in our study may be explained by finding debut JRA cases in the AAI group that could be solved under follow-up study. Low initial activity with following increasing activity under the treatment has to be suspected to the predisposition to the proliferative changes in the joint tissues required more intensive treatment.