Protective Immunity Remains Intact After Antibody Removal by Means of Proteasome Inhibition

Abstract

These data indicate that proteasome inhibitors plus plasmapheresis results in prolonged reduction of HLA antibodies while leaving protective immunity intact.

Reduction of alloantibodies via proteosome inhibition in cardiac transplantation

“…23 However, it is now clear that relapse (rebound DSA or new DSA formation) will occur in most patients, requiring these patients to undergo periodic HLA monitoring for the remainder of their transplant life. 24 Interestingly, this phenomenon of antibody rebound was also observed in our patients post-transplant although to date this has not translated into any clinically significant rejection episodes. Likewise, in desensitization, some early success has been seen in kidney transplantation with plasmapheresis/bortezomib use.…”

“…13,16 In addition, it has been shown to be clinically safe with sparing of protective plasma cellstherefore, at least in patients treated with one or two cycles, revaccination is not necessary. 24 To date, no randomized clinical trials have been published on bortezomib, although its use has recently become more widespread. 25 In addition to kidney transplantation, cases have been described in lung, 26 pancreas, 27 heart 28 and multiviceral 29 transplantation.…”

Transplanting Against Histocompatibility Barriers

“…This agent is now being used to attempt reduction of DSA in sensitized patients [92,93]. While many centers have incorporated this agent into treatment of AMR [94][95][96], its use for immunomodulation is limited to case reports. There have been 2 case reports that examined the use of bortezomib as a desensitizing agent pre-transplant.…”

Desensitization and Induction Immunosuppressive Therapy in Highly HLA-Sensitized Patients Receiving Cadaveric Renal Allograft)

“…By nearly 14 days after treatment, DSA levels had dropped significantly as well as repeat biopsy showed faint peritubular capillary C4d labeling and decreased glomerular C4d deposition. Trivedi et al (Trivedi et al, 2009(Trivedi et al, , 2010 reported thirteen living donor renal transplant patients treated with bortezomib one to two cycles and plasmapheresis to remove HLA antibodies posttransplant. All patients treated with bortezomib/plasmapheresis resulted in a primary DSA reduction of more than 50% measured by means of single antigen bead on Luminex.…”