title: 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.
authors.affiliation: a Research Laboratories and Academic Division of Clinical Rheumatology, Postgraduate School of Rheumatology, Department of Internal Medicine , University of Genova , Genova , Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: a Research Laboratories and Academic Division of Clinical Rheumatology, Postgraduate School of Rheumatology, Department of Internal Medicine , University of Genova , Genova , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
authors.affiliation: a Research Laboratories and Academic Division of Clinical Rheumatology, Postgraduate School of Rheumatology, Department of Internal Medicine , University of Genova , Genova , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paolino
authors.affiliation: a Research Laboratories and Academic Division of Clinical Rheumatology, Postgraduate School of Rheumatology, Department of Internal Medicine , University of Genova , Genova , Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pizzorni
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D060908:CTLA-4 Antigen
keywords: B lymphocytes; CD80/CD86; CTLA-4-Ig; Rheumatoid arthritis; T lymphocytes; abatacept; costimulatory molecules; endothelial cells; macrophages; osteoclasts