Pro-MMP levels and severity of RA

Objective

The aim of the present study was to analyze the relationship between systemic levels of proMMP3, MMP8, and MMP9 and MMP activity in α2M/MMP complexes and the progression of joint destruction in patients with early rheumatoid arthritis (RA).

Methods

One hundred and nine patients diagnosed with probable or definite RA of recent onset were entered in this study. The patients were followed up for 2 years; clinical data, blood samples and radiographs were obtained at baseline, at 1 year and at 2 years. MMP levels were quantified using ELISA and MMP activity assays.

Results

During the 2-year study, joint damage progressed from 0 to 10 (median Sharp score, P < 0.001) and the Disease Activity Score (DAS) decreased from 3.4 to 2.5 (P < 0.001). Stable levels of proMMP3 and α2M/MMP and a significant decrease in proMMP8 and proMMP9 levels was observed throughout the 2 years. Regression analysis showed that serum proMMP3 levels at the disease onset were independently associated with the progression of joint damage (B: 0.37, 95% CI 0.13–0.61, P = 0.003).

On the basis of the rate of joint destruction, the patients were divided into two subgroups: according to whether the progression of joint damage was mild or severe. The proMMP3 levels were significantly higher in the severe vs mild group at all time points. Mild progressors showed a decrease in the levels of proMMP8, proMMP9 and α2M/MMP complexes (P = 0.01 and P < 0.001, P = 0.009, respectively), whereas no changes in proMMP8, proMMP9 and α2M/MMP levels were found in the severe group.

Conclusion

ProMMP3 levels at the onset of disease are predictive of joint damage progression.