Advances in CTLA-4-Ig-mediated modulation of inflammatory cell and immune response activation in rheumatoid arthritis

Autoimmun Rev. 2013 May;12(7):758-67. doi: 10.1016/j.autrev.2013.01.001. Epub 2013 Jan 20.


Rheumatoid arthritis (RA) is a multifactorial and polygenic immune-mediated disease, the pathogenesis of which involves different cell types. T and B lymphocytes, macrophages, endothelial cells, fibroblasts and osteoclasts have all been implicated in mediating the production of autoantibodies, proinflammatory cytokines and ultimately bone erosions. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4-Ig, abatacept) is a unique biologic agent targeting the co-stimulatory molecules CD80/CD86, and is indicated for the treatment of moderate-to-severe RA in patients who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs, including methotrexate or anti-tumor necrosis factor agents. There is a growing body of evidence that, through selective modulation of the CD80/CD86 co-stimulatory molecules expressed by a variety of activated cell types, CTLA-4-Ig may inhibit the pathogenic RA process at several levels, both directly and indirectly. Here, we provide an overview of recent mechanistic studies of the action of CTLA-4-Ig on different cell types involved in mediating inflammation and joint damage in RA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / immunology
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / therapeutic use*
  • Humans
  • Immunoglobulins / immunology
  • Immunoglobulins / therapeutic use*
  • Inflammation / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use


  • Antirheumatic Agents
  • CTLA-4 Antigen
  • Immunoglobulins
  • Recombinant Proteins