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Comparison of knee joints with small joints: implications for pathogenesis and evaluation of treatment in rheumatoid arthritis


Serial synovial biopsy samples are increasingly used for the evaluation of novel therapies for rheumatoid arthritis (RA). Most studies have used knee biopsies, but technical improvements have made serial small joint arthroscopy feasible as well. Theoretically, there could be differences in the features of synovial inflammation between various joints as a result of mechanical factors, differences in innervation, and other factors. Therefore, we compared the cell infiltrate in paired synovial biopsies from inflamed knee joints with inflamed small joints obtained simultaneously in RA patients.

Materials and methods

Nine RA patients with both an inflamed knee joint and an inflamed small joint (wrist or metacarpophalangeal) were subjected to an arthroscopic synovial biopsy of both joints on the same day. Multiple biopsy specimens were collected and stained for macrophages, T cells, plasma cells, fibroblast-like synoviocytes, and interleukin(IL)-6 by immunohistochemistry. Sections were analyzed by digital image analysis.


The mean cell numbers for all investigated markers were equivalent in the samples from knee joints compared with the paired small joint samples. Statistical analysis by nonparametric tests identified no significant differences. Using Spearman Rank tests, we found significant correlations for the number of sublining macrophages (rho 0.817, P < 0.01), the number of T cells (rho 0.683, P < 0.05), and the number of plasma cells (rho 0.766, P < 0.02) when knee joints were compared with small joints. There was, however, no significant correlation for lining macrophages and fibroblast-like synoviocyte hyperplasia when large and small joints were compared.


The results presented in this study show that inflammation in one inflamed joint is generally representative for the process in other joints. Therefore, it is possible to use serial samples from the same joint selecting either large or small joints for evaluation of antirheumatic therapies. Hyperplasia of the intimal lining layer due to accumulation of intimal macrophages and fibroblast-like synoviocytes appears to depend in part on local factors.

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Kraan, M., Reece, R., Smeets, T. et al. Comparison of knee joints with small joints: implications for pathogenesis and evaluation of treatment in rheumatoid arthritis. Arthritis Res Ther 4 (Suppl 1), 35 (2002).

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