Microvascular inflammation (MVI) in kidney allografts in the absence of detectable donor-specific anti-HLA antibodies (DSA) is increasingly recognised as a cause of premature graft failure following kidney transplantation. Potential mechanisms include NK cell alloreactivity mediated by recognition of mismatched HLA class I molecules (missing-self) via killer-immunoglobulin-like receptors. Here, we report the case of an early kidney allograft rejection with severe MVI on biopsy in a patient that was fully HLA-matched except for a HLA-DPB1*04 mismatch in the donor. There were no detectable DSA at any time. MVI was successfully reversed and clinically stabilised with a 9-month course of daratumumab (anti-CD38 mAb). This case suggests alternative mechanisms of alloreactivity, such as NK cell-mediated effects, and highlights the existence of MVI in the absence of detectable B cell alloreactivity. Moreover, this case exemplifies the potential of anti-CD38 treatment in these patients.