Pathogenesis

Belimumab

Monoclonal antibody

Biology

CD34

Antibody

CD38

Autoantibody

Monoclonal

B-cell activating factor

Immunology

Plasma cell

Immunosuppression

Daratumumab

B cell

Stem cell

Antibody-dependent cell-mediated cytotoxicity

Genetics

Medicine

New England Journal of Medicine

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).

Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus