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Rheumatology 2001; 40: 367-374
© 2001 British Society for Rheumatology

Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies

M. D. Smith1,5,, M. C. Kraan4, J. Slavotinek2, V. Au2, H. Weedon5, A. Parker5, M. Coleman6, P. J. Roberts-Thomson3 and M. J. Ahern1

1 Departments of Medicine and
2 Radiology, Flinders Medical Centre,
3 Rheumatology Unit, Flinders Medical Centre, Adelaide, South Australia,
4 Department of Rheumatology, Amsterdam Medical Centre, Amsterdam, The Netherlands,
5 Rheumatology Unit and
6 Department of Pathology, Repatriation General Hospital, Daw Park, Adelaide, South Australia, Australia

Objectives. To document the change in synovial membrane macrophage and T-lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission induced by disease-modifying anti-rheumatic drugs (DMARDs).

Methods. Arthroscopic synovial biopsies were taken from four to seven sites around a knee joint in 13 patients with RA before and at regular intervals after commencing treatment with a DMARD. The cellular content of synovial membrane biopsies taken at regular intervals for a period of up to 3 yr after commencing treatment was quantitated by routine histopathology and immunohistochemical labelling with anti-macrophage (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were quantitated with a validated semiquantitative scoring system and video image analysis.

Results. Nine patients obtained clinical remission, as defined by American College of Rheumatology (ACR) criteria. The changes that occurred in the synovial biopsies included a reduction in lining layer thickness, reduced vascularity and cellular infiltrate. The most significant reduction in cellular infiltrate was in the lining layer macrophages, with less dramatic change in the subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro-positive T lymphocytes in the synovial membranes of patients who attained ACR-defined disease remission, it was less significant than the reduction in macrophage content of the synovial membranes and tended to plateau at a reduced level of T-cell infiltration.

Conclusions. Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.

KEY WORDS: Rheumatoid arthritis, Synovial membrane, Macrophages, T lymphocytes.

Correspondence to: M. D. Smith, Rheumatology Research Unit, Repatriation General Hospital, Daws Road, Daw Park, South Australia 5041, Australia.


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