Are autoantibodies the targets of B-cell-directed therapy?

B-cell-directed therapy-the use of agents that eliminate B cells or block cytokines important for B-cell function-is emerging as a promising approach to the treatment of rheumatic disease. Target diseases, including systemic lupus erythematosus (SLE), display diverse patterns of autoantibody production and aberrant activation of B cells. Despite the success of this general approach, the mechanisms by which B-cell-directed therapy ameliorates disease, and the role of autoantibodies as biomarkers of clinical response remain unclear. Importantly, although B-cell-directed therapy can reduce the production of some autoantibodies, the effects can be variable and heterogeneous, probably reflecting the critical (but ill-defined) roles of different B-cell and plasma cell populations in autoantibody production. Future studies during clinical trials of these agents are needed to define which B-cell and autoantibody populations are affected (or ought to be), and to discover informative biomarkers of clinical response that can be used to advance this therapeutic approach.

Duke Scholars

Author David Stephen Pisetsky Medicine, Rheumatology and Immunology