Effective and safe treatment of anti-CD38 therapy in systemic lupus erythematosus-associated refractory cerebral vasculitis induces immune tolerance.

Dear Editor, Autoimmunity is central to the pathogenesis of SLE. Autoantibodies, produced by short- and long-lived plasma cells, form immune complexes, deposit in target tissues, and drive systemic and organ-specific inflammation [1]. A major unmet need in SLE is to establish a curative treatment concept that would allow the elimination of autoreactive antibody-producing cells, the (re-)induction of immune tolerance and the achievement of a drug-free remission. CD20-targeted therapies may not affect all classes of autoantibodies, suggesting that SLE-specific autoantibodies derive from different sources, i.e. short- and long-lived plasma cells [2, 3]. Of note, long-lived plasma cells usually lack standard B cell markers such as CD20 and are therefore not affected by B cell–depleting therapy [4]. Hence long-lived plasma cells be of key importance in the treatment of patients with SLE who are refractory to conventional therapies. Daratumumab, a human monoclonal anti-CD38 antibody approved for the treatment of multiple myeloma [5], has been shown to reduce plasma cells in the bone marrow. In vitro studies and a case report in SLE have shown that anti-CD38 treatment with daratumumab can effectively target plasma cells and reduce disease activity in SLE [1, 6]. Here, we present a patient with SLE manifesting with cerebral vasculitis, who was successfully treated with daratumumab and in whom autoreactive antibody-producing cells seem to have been reduced.