Introduction: A major contributor to chronic allograft nephropathy is antibody-mediated rejection (AMBR) (Schinstock et al., 2020). Treatment includes escalation of immunosuppression and agents to remove antibody, reduce antibody production, or both. Rituximab is often used but not all antibody-producing cells express CD20. Bortezomib (BTZ - a proteasome inhibitor) induces apoptosis in many B-cell lineages, including plasma cells (Fichtner et al., 2025).
We report the safety and outcome of a post-transplant pediatric patient with strongly positive donor specific antibodies and graft dysfunction, who has received 3 courses of BTZ for ABMR.
Methods: A 7 year old African male received a deceased brain-death donor renal transplant for end stage kidney disease secondary to focal segmental glomerulosclerosis. Early disease recurrence was managed with B-cell depleting agents, steroids and plasmapheresis, with normalisation of graft function and remission of proteinuria. Two years post-transplant, graft function declined, with high levels of donor-specific antibody. Biopsy demonstrated acute on chronic AMBR. As B-cells remained depleted, we used plasmapheresis and BTZ - four doses of 1.3mg/m². Circulating DSA reduced markedly and graft function stabilised.
Recurrence of DSA and graft dysfunction prompted two further courses of BTZ at 62 and 71 months post-transplant
Results: Despite reduced B-cells, there was active ABMR with strong intensity of DSA. Targeting the broader B-cell lineage with BTZ reduced circulating DSA, and halted graft functional decline. No adverse effects were noted. Seven years post-transplant, graft function is 32mL/min/1.73m².
Conclusion: ABMR management in renal transplantation is not standardised, though B-cell depletion is often considered appropriate with detectable DSA. We report a case of repeated administrations of BTZ in a pediatric, B-cell deplete patient, demonstrating short-term safety and efficacy. In challenging cases of AMBR with B cell depletion, there may be a role for BTZ.

References:
Schinstock, C.A., Mannon, R.B., Budde, K., Chong, A.S., Haas, M., Knechtle, S., Lefaucheur, C., Montgomery, R.A., Nickerson, P., Tullius, S.G., Ahn, C., Askar, M., Crespo, M., Chadban, S.J., Feng, S., Jordan, S.C., Man, K., Mengel, M., Morris, R.E. and O’Doherty, I. (2020). Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group

Fichtner, A., Gauché, L., Süsal, C., Tran, T.H., Waldherr, R., Krupka, K., Guzzo, I., Carraro, A., Oh, J., Zirngibl, M., Weitz, M., König, J., Büscher, A., Berta, L., Simon, T., Awan, A., Rusai, K., Topaloglu, R., Peruzzi, L. and Printza, N. (2025). Incidence, risk factors, management strategies, and outcomes of antibody-mediated rejection in pediatric kidney transplant recipients-a multicenter analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN). Pediatric nephrology (Berlin, Germany)