Proteasome inhibition for recipient desensitization? A report of two sensitized kidney transplant candidates subjected to bortezomib treatment.

The proteasome inhibitor bortezomib was recently shown to effectively downregulate donor-specific humoral alloimmunity in rejecting kidney transplant recipients. The anti-humoral efficiency of proteasome inhibition in wait-listed non-immunosuppressed high risk patients is less well established. This pilot study, which included two pre-sensitized hemodialysis patients, was designed to get first insights into the impact of bortezomib treatment on allosensitization. Treatment consistent in two subsequent cycles of bortezomib. In an effort to increase responsiveness to treatment the second cycle was combined with dexamethasone. During a half-year follow-up, levels of CDC-PRA reactivity slightly decreased (patient 1: 87% to 80%, patient 2: 35% to 13%). However, proportions and MFI levels of detected Luminex SA reactivities (patient 1: N = 74; patient 2: N = 22) were not affected in a meaningful way. In parallel, bortezbmib treatment had no considerable effect on total immunoglobulin and kappa/lambda light chain levels. Our data suggest that, in absence of basal immunosuppression or rejection therapy, bortezomib may not or only modestly affect levels of humoral allosensitization. Future studies will have to clarify if additional anti-humoral measures or intensified treatment enhance the efficiency of proteasome inhibition as a desensitization strategy in advance of transplantation.