A closer look at rituximab induction on HLA antibody rebound following HLA incompatible kidney transplantation

Rituximab has been used to increase the efficacy of desensitization protocols for HLA incompatible kidney transplantation, however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with or 25 without rituximab induction, to determine the impact of B cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor specific antibodies (DSAs) and 33% of non-DSAs) compared to a control cohort desensitized and transplanted without rituximab (32% DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab treated patients, of the 39 HLA antibodies that increased post-transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B cell depletion. Compared to controls, rituximab-treated patients had a significantly greater mean reduction in DSA (−2505 versus −292 mean fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab treated and 40% in non-treated recipients). Thus, rituximab induction in HLA incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not impact DSA elimination, antibody mediated rejection, or 5 year allograft survival when compared to recipients desensitized and transplanted without rituximab.