Cathepsin B and its endogenous inhibitor cystatin C in rheumatoid arthritis synovium

OBJECTIVE: To compare the expression of cathepsin B and its endogenous inhibitor cystatin C in synovial tissue of patients with rheumatoid arthritis (RA) and to determine the cell type expressing cystatin C. METHODS: The expression of cathepsin B and cystatin C was studied by immunohistochemistry in synovial tissue of 10 patients with RA and compared to healthy controls. Applying double labeling methods, the expression of cathepsin B was compared to that of cystatin C. To determine the cell type expressing cystatin C, double labeling with anti-CD68 (PG-M1) was performed. RESULTS: Both cystatin C and cathepsin B were strongly expressed in synoviocytes of patients with RA. Furthermore, fibroproliferative tissue at the site of cartilage and bone destruction contained fibroblast-like and macrophage-like cells positive for cystatin C and cathepsin B, whereas normal synovial tissue exhibited only limited expression of these molecules. Osteoclasts revealed positive staining for CD68 and cystatin C, but not for cathepsin B. CONCLUSION: Cystatin C is a product of both macrophage-like and fibroblast-like synoviocytes. The strong expression of both the matrix degrading cysteine proteinase cathepsin B and the cysteine proteinase inhibitor cystatin C in rheumatoid synovium, particularly at the sites of bone and cartilage erosion, suggests that cystatin C--although increased--is not sufficient to prevent matrix degradation by cathepsin B.