BAFF- and APRIL-targeted therapy in systemic autoimmune diseases.

B cells play a pivotal role in autoimmunity not only by producing pathogenic autoantibodies but also by modulating immune responses via the production of cytokines and chemokines. The B cell-activating factor/a proliferation-inducing ligand (BAFF/APRIL) system promotes B cell survival and differentiation and thus plays a prominent role in the pathogenesis of autoimmune diseases. Currently, BAFF and APRIL inhibitors are in clinical trials for systemic lupus erythematosus with significant efficacy. However, several studies have demonstrated the efficacy of the BAFF/APRIL blockade which showed considerable variability in the response to B cell-targeted therapy. This may indicate substantial heterogeneity in the pathogenesis of autoimmune diseases. Therefore, objective markers that can predict the effect of BAFF/APRIL-blocking agents could be valuable to the precision medicine linked clinically and to cost-effective therapy.