Relevance of lymphocyte subsets to B cell-targeted therapy in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with heterogeneous clinical manifestations, and pathologically characterized by activation of autoreactive T cells and overproduction of autoantibodies by B cells. Although corticosteroids and immunosuppressants are widely used for the treatment, safer and more effective therapies are needed. B cells play a pivotal role in the pathogenesis of SLE not only by producing pathogenic autoantibodies but also by modulating immune responses via production of cytokines and chemokines. The potential efficacy of B-cell depletion therapy has been reported in SLE. Treatment with rituximab, an anti-CD20 antibody, results in reconstitution of B cells in the periphery, thereby inhibiting T cell activation and differentiation, which in turn leads to long-term remission of SLE. However, we have reported SLE recurrence driven by B cell- or T cell-memory activation after long-term remission, demonstrating pathological heterogeneity in SLE. Ideally, differential targeting therapies should be considered according to relevant lymphocyte subsets. Therefore, evaluation of peripheral blood lymphocyte subsets could be valuable for predicting the response to B cell-targeted therapy. A better understanding of B cell pathology should contribute to the development of novel specific therapies for SLE.