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Basic and translational research
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Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimumab
  1. M M J Herenius1,
  2. R M Thurlings1,
  3. C A Wijbrandts1,
  4. R J Bennink2,
  5. S E Dohmen3,
  6. C Voermans3,
  7. D Wouters4,
  8. E S Izmailova5,
  9. D M Gerlag1,
  10. B L F van Eck-Smit2,
  11. P P Tak1
  1. 1Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Experimental Immunohematology, Landsteiner Laboratory, Sanquin Research, Amsterdam, The Netherlands
  4. 4Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands
  5. 5Department of Research and Development, Millennium Pharmaceuticals, Cambridge, Massachusetts, USA
  1. Correspondence to P P Tak, Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, F4-105, PO Box 22700, 1100 DE Amsterdam, The Netherlands; p.p.tak{at}amc.uva.nl

Abstract

Objectives The mechanism of action of treatment with tumour necrosis factor (TNF) blockers in rheumatoid arthritis (RA) is still not completely understood. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium.

Methods A novel technique was used to analyse the migration of labelled autologous monocytes before and 14 days after initiation of adalimumab treatment using scintigraphy. CD14 monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labelled with technetium-99m-hexamethylpropylene-amino-oxime. Scintigraphic scans were made 1, 2 and 3 h after re-infusion.

Results As early as 14 days after the start of treatment with adalimumab a significant decrease in disease activity score evaluated in 28 joints was shown. There was no significant decrease in the influx of monocytes into the joint at this time.

Conclusions This study indicates that adalimumab treatment does not reduce the influx of monocytes into the synovium early after initiation of treatment. As previous studies showed a rapid decrease in macrophage infiltration after TNF-antibody therapy, which could not be explained by increased cell death, this points to an important role for enhanced efflux of inflammatory cells from the synovium.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

https://doi.org/10.1136/ard.2010.141549

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    Footnotes

    • Funding This study was funded by Millennium: The Takeda Oncology Company.

    • Competing interests Millennium: The Takeda Oncology Company participated in the design of the study, monitored the clinical study and participated in the analysis and interpretation of the clinical study.

    • Ethics approval This study was conducted with the approval of the Academic Medical Center/University of Amsterdam.

    • Provenance and peer review Not commissioned; externally peer reviewed.