Rapid Interaction Between CTLA4-Ig (Abatacept) and Synovial Macrophages from Patients with Rheumatoid Arthritis

Abstract

To the Editor: We have demonstrated that macrophages could be considered one of the main direct target cells for treatment with CTLA4-Ig (abatacept) in patients with rheumatoid arthritis (RA), in mixed cultures of macrophages and activated T cells, or in primary single cultures of RA synovial macrophages1,2,3. Previous studies showed that a significant downregulation of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and IL-6 was evident for cultured human macrophages treated with CTLA4-Ig, through direct interaction with B7 molecules on the surface of RA synovial macrophages at 24 h1. The interaction between CTLA4-Ig and B7 molecules (CD80/CD86) masked their expression on RA synovial macrophages1. From those results, we carried out further evaluations of cytokine production and modulation in RA synovial macrophage primary cultures at the gene expression level and after different short-term CTLA4-Ig treatments (3 and 12 hours), to further investigate the timing of the interaction of CTLA4-Ig and synovial macrophages. As well, we analyzed transforming growth factor-β (TGF-β) gene expression and production. Synovial macrophages were obtained, with informed … Address correspondence to Prof. M. Cutolo; E-mail: mcutolo{at}unige.it