Effective and safe treatment of anti-CD38 therapy in systemic lupus erythematosus–associated refractory cerebral vasculitis induces immune tolerance
Melek Yalçın Mutlu, Jochen Wacker, Koray Taşçılar, Jule Taubmann, Bernhard Manger, Gerhard Krönke, Georg Schett, David Simón
Abstract
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.