Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis

Arthritis Rheum. 2013 Mar;65(3):599-607. doi: 10.1002/art.37787.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / metabolism
  • Antigen-Presenting Cells / pathology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology*
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / drug effects*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immunoconjugates / therapeutic use*
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / pathology*


  • Antirheumatic Agents
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Cell Adhesion Molecules
  • Immunoconjugates
  • Lipopolysaccharide Receptors
  • Abatacept