Document Detail

Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis.
MedLine Citation:
PMID:  23203906     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
M Bonelli; E Ferner; L Göschl; S Blüml; A Hladik; T Karonitsch; H P Kiener; R Byrne; B Niederreiter; C W Steiner; E Rath; M Bergmann; J S Smolen; C Scheinecker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-24     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  599-607     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Antigen-Presenting Cells / drug effects,  metabolism,  pathology
Antigens, CD14 / metabolism
Antigens, CD80 / metabolism
Antigens, CD86 / metabolism
Antirheumatic Agents / therapeutic use
Arthritis, Rheumatoid / drug therapy*,  pathology*
Cell Adhesion Molecules / metabolism
Cell Movement / drug effects*
Human Umbilical Vein Endothelial Cells
Immunoconjugates / therapeutic use*
Middle Aged
Monocytes / drug effects*,  metabolism,  pathology*
Reg. No./Substance:
0/Antigens, CD14; 0/Antigens, CD80; 0/Antigens, CD86; 0/Antirheumatic Agents; 0/CD86 protein, human; 0/Cell Adhesion Molecules; 0/Immunoconjugates; 7D0YB67S97/abatacept

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