Anti-CD20 therapy in SLE patients: what can we learn from the B cells- repopulation phase. (360G-Wellcome-090406_Z_09_Z)

What is the mechanism of action of B cell depletion in the context of SLE? Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease significantly affecting both the quality of life and life expectancy of suffers. Recently, a number of groups, including our own, have reported the efficacy of treating SLE patients with rituximab, a monoclonal antibody that targets CD20 and leads to significant B cell depletion. While there is growing evidence that B cell depletion has an effect on T c ell activation, the immunological mechanisms related to the therapeutic effect of rituximab remain to be fully elucidated. For this study we propose to investigate the effect of rituximab treatment on subsequently repopulating B cells, and the effect of these B cells on T cell activation and differentiation, in patients who respond to B cell depletion and those who do not. The key goals of this research are to further understanding of how rituximab treatment works and the antibody-independent co ntribution of B cells to SLE.