Daratumumab for antibody-mediated rejection: Is it time to target the real culprit?

Am J Transplant. 2023 Dec;23(12):1990-1994. doi: 10.1016/j.ajt.2023.06.018. Epub 2023 Jul 4.

Abstract

We report the case of a sensitized woman who underwent successful transplantation after a desensitization protocol, with an optically normal 8-day biopsy. At 3 months, she developed active antibody-mediated rejection (AMR) due to preformed donor-specific antibodies. It was decided to treat the patient with daratumumab, an anti-CD38 monoclonal antibody. The mean fluorescence intensity of donor-specific antibodies decreased, pathologic signs of AMR regressed, and kidney function returned to normal. A molecular assessment of biopsies was retrospectively performed. By doing so, regression of the molecular signature of AMR was evidenced between the second and third biopsies. Interestingly, the first biopsy revealed a gene expression profile of AMR, which helped retrospectively classify this biopsy as AMR, illustrating the relevance of molecular phenotyping of biopsy in high-risk situations such as desensitization.

Keywords: antibody-mediated rejection; antibody-secreting cells; daratumumab; immunosuppressive therapy; kidney transplantation; molecular diagnosis.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Biopsy
  • Female
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Humans
  • Isoantibodies / adverse effects
  • Kidney Transplantation* / adverse effects
  • Retrospective Studies

Substances

  • daratumumab
  • Isoantibodies
  • Antibodies, Monoclonal