B Cells in RA & Mechanism of Action of MabThera® (rituximab)
Rheumatoid arthritis (RA) is a destructive inflammatory disease, to which B cells make a significant contribution. B cells have at least three critical roles in the pathophysiology of RA: antigen presentation leading to T cell activation, autoantibody production and pro-inflammatory cytokine production (Shaw et al. 2003). The important role that B cells play in the development of rheumatoid arthritis is confirmed by the effectiveness of selectively targeting B cells with MabThera® (rituximab) (Cohen et al. 2006).
MabThera binds specifically to a unique cell-surface marker CD20, which is found on a subset of B cells but not on stem cells, pro-B cells, plasma cells or any other cell type.
As a result, B cell populations recover after MabThera treatment and acquired immunity is left intact (Edwards et al. 2004; Shaw et al. 2003; Silverman et al. 2003; Sell & Max 2001; Roitt et al. 2001; Cohen et al. 2006).
CD20 is expressed on mature B cells providing a target for MabThera. When MabThera binds to CD20 it activates one of the following three mechanisms that contribute to selective B cell depletion: cell-mediated cytotoxicity, complement-activated B cell lysis or apoptosis. Overall, selective B cell therapy removes a direct source of activation signal for inflammatory cells and inhibits the inflammatory process in rheumatoid arthritis. (Shaw et al. 2003).