Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Monocyte Migration to the Synovium in Rheumatoid Arthritis Patients Treated with Adalimumab.
Herenius3, Marieke, Thurlings4, Rogier, Wijbrandts4, Carla, Bennink5, Roelof, Dohmen6, Serge, Voermans6, Carlijn, Wouters2, Diana
Academic Med Ctr/Univ of Amsterdam, Amsterdam, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, Noord Holland, The Netherlands
Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Division of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Landsteiner Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands
Millennium Pharmaceuticals, Inc, Department of Research and Development, Cambridge, MA
The mechanism of action of treatment with tumor necrosis factor a (TNF-a) blockers in rheumatoid arthritis (RA) is still not completely understood. Since the recognition of synovial tissue as the primary site of inflammation, studying the synovium has provided insight into the pathogenesis of the disease and the mechanism of action of different therapies. Anti-TNF antibody treatment has been shown to result in marked reduction of synovial inflammation in both RA and psoriatic arthritis early after initiation of therapy. This early reduction in synovial inflammation could not be explained by apoptosis induction at the site of inflammation. This leaves either reduced cell influx or enhanced cell efflux to explain this process. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium.
We used a novel technique to analyze the migration of labelled autologous monocytes using scintigraphy. CD14+ monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labeled with 99mTc-HMPAO. Scintigraphic scans were made 1 hour, 2 hours and 3 hours after re-infusion. This procedure was performed at three time points with a two weeks interval. Adalimumab treatment was started after the second set of scans.
Re-infusion lead to a stable number of monocytes in the joint of interest after 1, 2 and 3 hours on all days. Already 14 days after the start of treatment with adalimumab a significant decrease in DAS28 was shown. There was no significant change in monocyte influx 1, 2 and 3 hours after re-infusion from day -14 to day 1, which was before the start of adalimumab treatment (p=0.33, p = 0.67, p=0.21, respectively). Of interest, the influx of monocytes did not decrease after re-infusion of monocytes comparing day 14 to baseline, indicating that adalimumab treatment did not affect the influx of monocytes early after initiation of treatment.
The results of this mechanistic study indicate that CD14+ monocyte influx into the synovium is not altered two weeks after the start of adalimumab treatment. As previous studies showed a rapid decrease in macrophage infiltration after anti-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. These data are in line with the recent observation that monocytes migrate towards the inflamed RA synovium at a slow macrophage-replacement rate and with the recently shown increase in lymphatic vessels in the synovium after TNF-a blockade.
To cite this abstract, please use the following information:
Herenius, Marieke, Thurlings, Rogier, Wijbrandts, Carla, Bennink, Roelof, Dohmen, Serge, Voermans, Carlijn, et al; Monocyte Migration to the Synovium in Rheumatoid Arthritis Patients Treated with Adalimumab. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1822