Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression.
Jørgensen I., Kos J., Krašovec M., Troelsen L., Klarlund M., Jensen TW., Hansen MS., Jacobsen S., DRD study group None., TIRA study group None.
This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein. Erosive status of hands and wrists was expressed by the Larsen score and recorded at inclusion and after 1 year. Serum levels of cathepsin B, cathepsin H, stefin A, stefin B, and cystatin C were determined by enzyme-linked immunosorbent assay. Neither cathepsin B nor cathepsin H serum levels were associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum levels of cystatin C. Progression of radiographic destruction was associated with high serum levels of C-reactive protein, stefin A and B, whereas serum levels of cystatin C were not associated with radiographic progression. The findings in this study support further investigation in the regulation of the activity of cathepsins and their inhibitors in erosive rheumatoid arthritis.