CTLA-4 blockade in the treatment of rheumatoid arthritis: an update

ABSTRACT

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation as well as by extra-articular involvement. The immunopathology of RA is polygenic and involves different cell populations. Patients with an inadequate response to non-biologic disease- modifying antirheumatic drugs (DMARDs) should integrate their therapy with biologic DMARDs. Biologic DMARDs can target several inflammatory cytokines, or CD20+ B cells, or can modulate T-cell co-stimulation and activation. The cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4-Ig: abatacept) that selectively modulates the CD28:CD80/86 co-stimulation signal appears a biologic DMARD interacting with T cells but also with other cell populations involved in RA pathophysiology. Activated B lymphocytes, macrophages, osteoclasts and endothelial cells express the costimulatory molecules (CD80/86) and are downregulated by CTLA-4 blockade. The relatively low frequency and severity of safety issues related to CTLA-4-Ig treatment seems further to confirm the targeted downregulatory action exerted by the fusion protein, which is mainly focussed on activated immune/inflammatory cells.

KEYWORDS:

• Rheumatoid arthritis
• costimulatory molecules
• CTLA-4-Ig
• T lymphocytes
• B lymphocytes
• osteoclasts
• macrophages
• endothelial cells
• abatacept
• CD80/CD86

Acknowledgments

The authors would like to thank Dr. Sara De Gregorio from our Division of Rheumatology for her support in the graphical data representation.

Financial & competing interests disclosure

M Cutolo has received financial support for clinical and laboratory research (funds to the University of Genova) from Bristol-Myers Squibb. M Cutolo has also received fund support from Actelion and Horizon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.