[Progress in B cell targeting therapy for the treatment of systemic lupus erythematosus]
Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease characterized by multi organ manifestation. Although the etiology of the disease remains unclear, the activation of autoreactive T cells and production of antibodies by B cells are mainly involved in the pathological processes of the disease. B cell depletion therapy using anti CD20 antibody rituximab has shown a rapid onset of effect and prolonged efficacy in refractory SLE, emerging as a promising new agent for the treatment of SLE. We also reported that rituximab is safe for the treatment of active SLE in a domestic pilot study and a multi center phase I/II clinical trial. In regard to the mechanism underlying the efficacy of rituximab, it has been reported that the drug caused peripheral depletion of memory B cells and plasma cells. We found that rituximab efficiently depleted naive and memory B cells and decreased co stimulatory molecules on B cells and memory T cells. Recovered B cells in patients in long term remission were dominated by naive B cells with an increased ratio of naive T cells, and co stimulatory molecules remained low. These findings indicate that the reconstitution of the B cell compartment results in the inhibition of T cell activation by memory B cells, which leads to the sustained remission of SLE by rituximab. Although the recent placebo controlled trials such as EXPLORER with rituximab in SLE did not achieve satisfactory results, other evidence continues to be published in support of the notion that B cell depletion could be useful for refractory SLE. In addition, other B cell targeted therapies, such as CD22 and agents that interrupt B T cell interaction, including belimumab, also have potential of the therapeutic application.
Journal of UOEH