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Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis
  1. J J Haringman1,
  2. D M Gerlag1,
  3. A H Zwinderman2,
  4. T J M Smeets1,
  5. M C Kraan1,
  6. D Baeten3,
  7. I B McInnes4,
  8. B Bresnihan5,
  9. P P Tak1,
  10. on behalf of the OMERACT Special Interest Group on Synovial Analysis in Clinical Trials
  1. 1Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, The Netherlands
  2. 2Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre/University of Amsterdam, The Netherlands
  3. 3Department of Rheumatology, Ghent University Hospital, Belgium
  4. 4Centre for Rheumatic Diseases, University of Glasgow, Scotland, UK
  5. 5Rheumatology Department, St Vincent’s University Hospital, Dublin, Ireland
  1. Correspondence to:
    Professor P P Tak
    Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands;


Background: Previous work identified synovial sublining macrophage numbers as a potential biomarker for clinical efficacy in rheumatoid arthritis.

Objective: To investigate the association between changes in infiltration of synovial macrophages and clinical improvement after antirheumatic treatment.

Methods: 88 patients who participated in various clinical trials were studied. All patients underwent serial arthroscopy before initiation of treatment and after different time intervals. Immunohistochemical and digital image analysis were performed according to standardised procedures to detect changes in CD68+ synovial sublining macrophages in relationship to changes in the 28 joint count Disease Activity Score (DAS28). Statistical analysis was performed using one way analysis of variance, the independent samples t test, linear regression, and the standardised response mean (SRM).

Results: For good, moderate, and non-responders, according to the DAS28 response criteria, there was a significant difference in the change in sublining macrophages (mean (SEM) cells/mm2 −643 (124), −270 (64), and −95 (60), respectively; p<0.0003). There was a significant correlation between the change in the number of macrophages and the change in DAS28 (Pearson correlation 0.874, p<0.01). The change in sublining macrophages explained 76% of the variation in the change in DAS28 (p<0.02). The sensitivity to change of the biomarker was high in patients treated actively (SRM >0.8), whereas the ability to detect changes in placebo treated patients was weak (SRM <0.3).

Conclusion: The results suggest that changes in synovial sublining macrophages can be used to predict possible efficacy of antirheumatic treatment.

  • DAS28, 28 joint count Disease Activity Score
  • DMARDs, disease modifying antirheumatic drugs
  • IL, interleukin
  • LEF, leflunomide
  • MTX, methotrexate
  • RA, rheumatoid arthritis
  • SRM, standardised response mean
  • ST, synovial tissue
  • TNF, tumour necrosis factor
  • arthroscopy
  • biomarkers
  • macrophages
  • rheumatoid arthritis
  • synovial tissue
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