The influence of bortezomib on donor specific antibody reduction in patients with antibody mediated rejection

Abstract

Renal allograft biopsy is the gold standard for monitoring and diagnosing antibody mediated rejection (AMR), yet a biopsy is invasive, expensive, and may result in complications. Monitoring antibodies may aid in diagnosing and monitoring AMR, although many questions remain unanswered regarding the clinical utility of antibody monitoring. The purpose of this review is to examine the influence of bortezomib on reduction of donor specific antibody after AMR in renal transplant recipients. A retrospective review of patients was performed. Patients who received bortezomib after suffering AMR refractory to intravenous immunoglobulin and plasmapheresis from 2009 to 2011 were selected. Seven patients were identified. Three patients had antibodies tested after IVIG treatment with a mean antibody lowering of 29 percent from baseline. Five of the seven patients had antibodies tested after bortezomib treatment and the mean antibody reduction was 47 percent from baseline. Four patients were biopsied after treatment and all were C4d negative. The other three patients were not biopsied. Renal function improved in most patients. One patient returned to dialysis 16 months after transplant and treatment and another patient died with a functioning graft, due to pneumonia five months after transplant and treatment. In these seven cases, the use of intravenous immune globulin, plasmapheresis, and bortezomib appear to decrease antibodies, improve renal function, and reverse histological markers for rejection. Long-term, prospective follow-up is warranted to determine the influence of bortezomib on donor antibody removal, histological changes, and graft survival.