title: Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Bonelli
authors.forename: E
authors.initials: E
authors.lastname: Ferner
authors.forename: L
authors.initials: L
authors.lastname: Göschl
authors.forename: S
authors.initials: S
authors.lastname: Blüml
authors.forename: A
authors.initials: A
authors.lastname: Hladik
authors.forename: T
authors.initials: T
authors.lastname: Karonitsch
authors.forename: H P
authors.initials: HP
authors.lastname: Kiener
authors.forename: R
authors.initials: R
authors.lastname: Byrne
authors.forename: B
authors.initials: B
authors.lastname: Niederreiter
authors.forename: C W
authors.initials: CW
authors.lastname: Steiner
authors.forename: E
authors.initials: E
authors.lastname: Rath
authors.forename: M
authors.initials: M
authors.lastname: Bergmann
authors.forename: J S
authors.initials: JS
authors.lastname: Smolen
authors.forename: C
authors.initials: C
authors.lastname: Scheinecker
mesh_terms: D000069594:Abatacept; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D018501:Antirheumatic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; D018950:Lipopolysaccharide Receptors; D000069594:Abatacept