Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix metalloproteinases in arthroscopic synovial biopsies: comparison with synovial samples from patients with end stage, destructive rheumatoid arthritis
- 1Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands
- 2Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
- 3Rheumatology Research Unit, Repatriation General Hospital, Daw Park, SA, Australia
- Correspondence to:
Dr T J M Smeets, Division of Clinical Immunology and Rheumatology, F4–218, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;
- Accepted 5 December 2002
Background: Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics.
Objective: To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA.
Methods: Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1β, IL6, tumour necrosis factor α (TNFα), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF.
Results: The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFα, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1β was on average higher in surgical samples.
Conclusion: Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1β in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1β in cartilage and bone destruction.
- DMARDs, disease modifying antirheumatic drugs
- FLS, fibroblast-like synoviocytes
- HRP, horseradish peroxidase
- IL, interleukin
- mAb, monoclonal antibody
- MMPs, matrix metalloproteinases
- RA, rheumatoid arthritis
- ST, synovial tissue
- TIMP, tissue inhibitor of metalloproteinase
- VEGF, vascular endothelial growth factor