title: Advances in CTLA-4-Ig-mediated modulation of inflammatory cell and immune response activation in rheumatoid arthritis.
abstract: 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.
authors: Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy. mcutolo@unige.it
authors: Maurizio
authors: M
authors: Cutolo
authors: Steven G
authors: SG
authors: Nadler
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D060908:CTLA-4 Antigen / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D060908:CTLA-4 Antigen; D007136:Immunoglobulins; D011994:Recombinant Proteins