ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2163

Abatacept Monotherapy Effectively Reduces the Frequency of Osteoclast Precursor Cells in the Peripheral Blood of Patients with Rheumatoid Arthritis and Inhibits Their Differentiation Into Osteoclasts

Sandra Mueller-Schmucker1, Roland Axmann1, Sonja Herman2, Mario Zaiss1, Manuela Le Bars3, Thomas Harrer1 and Georg A. Schett4, 1University of Erlangen-Nuremberg, Erlangen, Germany, 2Rheumatology, Medical University of Vienna, Vienna, Austria, 3Bristol-Myers Squibb, Rueil Malmaison, France, 4Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Bone resorbing osteoclasts origin from monocytes. We have recently shown that binding of abatacept (CTLA4-Ig) to CD80 and CD86 on the surface of monocytes blocks their differentiation into osteoclasts in vitro (Axmann et al, Ann Rheum Dis. 2008;67:1603-9). We thus speculated whether abatacept therapy impairs the potential of osteoclast differentiation in rheumatoid arthritis patients in vivo.

Methods:

We compared the frequency of CD11b+CD115+ osteoclast precursor cells in the peripheral blood of 60 patients with rheumatoid arthritis (RA), either untreated (N= 15) or treated with methrotrexate (N=15), adalimumab (N= 15) or abatacept as monotherapies (N=25) using FACS analysis. We also performed osteoclast differentiation assays from the peripheral blood mononuclear cells from these patients to quantify osteoclast differentiation and to test for osteoclast gene expression profiles. 

Results:

The frequency of osteoclast precursors in the peripheral blood was significantly (p< 0.01) lower in abatacept treated patients (82,4 ± 1,8%) than in untreated controls (97,4 ± 0,6%), whereas no significant differences between controls and adalimumab and methotrexate treated patients, respectively, were found. In addition, osteoclast differentiation from peripheral blood was impaired in abatacept-treated patients (mean osteoclast number per well= 32,5) as compared to untreated controls (mean osteoclast number per well= 145,6). In addition, sequential analysis of patients before and after abatcept exposure showed reduced potential of osteoclast precursors to differentiate into osteoclasts after the exposure to abatacept. Moreover, we found significant down regulation of essential osteoclast differentiation factors c-Fos and NFAT1c after in vitro exposure of monocytes to abatacept. 

Conclusion:

Abatacept treatment decreases osteoclast precursor cell frequency in RA patients as well as osteoclast differentiation potential of peripheral blood mononuclear cells. Moreover, abatcept leads to a down regulation of key osteoclast genes such as c-Fos and NFATc1. These data explain the mechanism by which abatcept may achieve bone protection during the treatment of RA patients.

Disclosure:

S. Mueller-Schmucker,
None;

R. Axmann,
None;

S. Herman,
None;

M. Zaiss,
None;

M. Le Bars,

BMS,

3;

T. Harrer,
None;

G. A. Schett,
None.

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