Dr. Smolen has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb (less than $10,000) and a research grant from Bristol-Myers Squibb.
Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis
Version of Record online: 25 FEB 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 3, pages 599–607, March 2013
How to Cite
Bonelli, M., Ferner, E., Göschl, L., Blüml, S., Hladik, A., Karonitsch, T., Kiener, H. P., Byrne, R., Niederreiter, B., Steiner, C. W., Rath, E., Bergmann, M., Smolen, J. S. and Scheinecker, C. (2013), Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis. Arthritis & Rheumatism, 65: 599–607. doi: 10.1002/art.37787
- Issue online: 25 FEB 2013
- Version of Record online: 25 FEB 2013
- Accepted manuscript online: 30 NOV 2012 04:06PM EST
- Manuscript Accepted: 1 NOV 2012
- Manuscript Received: 2 FEB 2012
- Österreichische Nationalbank—Jubiläumsfond. Grant Number: 12754
- European Union Seventh Framework Programme (project Masterswitch). Grant Number: HEALTH-F2-2008-223404
- Innovative Medicines Initiative Joint Undertaking. Grant Number: 115142 (BTCure)
The binding of abatacept (CTLA-4Ig) to the B7 ligands CD80 and CD86 prevents the engagement of CD28 on T cells and thereby prevents effector T cell activation. In addition, a direct effect of CTLA-4Ig on antigen-presenting cells (APCs) could contribute to the therapeutic effect. To further elucidate the mechanism of CTLA-4Ig, we performed phenotype and functional analyses of APCs in patients with rheumatoid arthritis (RA) before and after the initiation of CTLA-4Ig therapy.
Peripheral blood mononuclear cells were analyzed before and at 2 and 4 weeks after the initiation of CTLA-4Ig therapy. Proportions of APCs were determined by flow cytometry. CD14+ monocytes were further analyzed for the expression of costimulatory and adhesion molecules and for their transendothelial migratory capacity in vitro. In addition, CD14+ monocytes from healthy controls were analyzed for their migratory and spreading capacity.
Proportions and absolute numbers of monocytes were significantly increased in RA patients treated with CTLA-4Ig. The expression of several adhesion molecules was significantly diminished. In addition, monocytes displayed a significant reduction in their endothelial adhesion and transendothelial migratory capacity upon treatment with CTLA-4Ig. Likewise, isolated monocytes from healthy controls revealed a significant reduction in their migratory and spreading activity after preincubation with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies.
We describe direct effects of CTLA-4Ig therapy on phenotype and functional characteristics of monocytes in RA patients that might interfere with the migration of monocytes to the synovial tissue. This additional mechanism of CTLA-4Ig might contribute to the beneficial effects of CTLA-4Ig treatment in RA patients.