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

We report the case of a sensitised woman successfully transplanted after a desensitisation protocol, with an optically normal 8-day biopsy. At 3 months, she developed an 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. DSA MFI decreased, pathological signs of AMR regressed, and kidney function returned to normal. Molecular assessment of biopsies was retrospectively performed. By doing so, regression of molecular signature of AMR was evidenced between the 2nd and the 3rd biopsy. Interestingly, the first biopsy had a gene expression profile of AMR, which retrospectively classified this biopsy as an AMR, illustrating the relevance of molecular phenotyping of biopsy in high-risk situations, such as desensitisation.