Targeting CD38 in subclinical antibody-mediated rejection in HLA-incompatible kidney transplantation: a case report

Presensitized patients with donor-specific antibodies (DSAs) are at increased risk of antibody-mediated rejection (AMR) of kidney allografts. The long-term consequences of AMR are serious because currently available therapeutic options lack lasting effectiveness. Targeting plasma cells to counter antibody production may hold promise for treating AMR. Daratumumab is a fully humanized monoclonal antibody directed against CD38, a glycoprotein expressed at high levels on plasma cells and, in addition, natural killer cells, which are suggested to act as effector cells in AMR. Several case reports suggested its efficacy in the treatment of AMR in patients with and without multiple myeloma. Timing of such therapy is of significant concern because serum creatinine alone cannot distinguish subclinical injury, and innovative tools are necessary for more precise diagnostics. Here, we describe a case of severe DSA rebound associated with subclinical AMR by histology and molecular assessments effectively reversed by a 6-mo course of daratumumab.