TY - JOUR T1 - Rheumatoid Arthritis Clinical Benefits from Abatacept, Cytokine Blockers, and Rituximab Are All Linked to Modulation of Memory B Cell Responses JF - The Journal of Rheumatology JO - J Rheumatol SP - 825 LP - 828 DO - 10.3899/jrheum.140022 VL - 41 IS - 5 AU - GREGG J. SILVERMAN AU - ADAM PELZEK Y1 - 2014/05/01 UR - http://www.jrheum.org/content/41/5/825.abstract N2 - Abatacept (ABA) is a biologic agent with great proven efficacy in patients with rheumatoid arthritis (RA)1. At a molecular level, ABA is composed of recombinant domains of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), fused to the constant region domains of human IgG1, which serves to increase in vivo half-life. This agent binds to CD80/CD86 with a much higher avidity than the CD28 on many T cells, and therefore can act as a physiologic competitive inhibitor that interrupts cell-cell co-stimulatory interactions. In earlier reports, ABA treatment of patients with RA was shown to have striking effects on the modulation of T cell subsets2.The recent report by Scarsi, et al highlights the bidirectional nature of the CD28-CD80/86 interaction and the profound effects that ABA can have on the B cell compartment of the immune system, especially for memory B cells3. With the proven efficacy of the B cell-targeted anti-CD20 agent rituximab (RTX), the central roles of B cells in RA have become well accepted, and B cells also commonly express the co-stimulatory molecules CD80/864. Even at the earliest onset of clinical signs and symptoms, patients with RA display dysregulated immune-cell trafficking and maturation. Compared to healthy subjects, patients with RA also have abnormal levels of circulating memory B cells (identified by CD27 expression), and this may in part reflect their recruitment to the synovial compartment or secondary lymph nodes5.In a small study of 28 patients with RA, Scarsi, et al showed that after 6 months of ABA treatment, patients with clinical responses had significant decreases in levels of switched memory B cells, with persistent decreases in memory B cell subsets also found at 12 months3. ABA therapy also significantly reduced levels of serum total IgG, IgA, and IgM, … Address correspondence to Dr. G. Silverman, Department of Medicine, NYU School of Medicine, 450 E. 29th St., New York, New York 10016, USA. E-mail: Gregg.Silverman{at}nyumc.org ER -