Proteasome inhibitor-based therapy for antibody-mediated rejection

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Donor-specific anti-human leukocyte antigen antibodies (DSAs) critically impair long-term renal graft function and survival.
• Conventional therapies for antibody-mediated rejection (AMR) show limited efficacy due to incomplete depletion of antibody-producing plasma cells.

Purpose of the Study:

• To evaluate the efficacy of proteasome inhibition (PI) as a novel therapeutic strategy for AMR in renal transplantation.
• To assess the ability of PI to deplete plasma cells, reduce DSA levels, and improve allograft outcomes.

Main Methods:

• Review of initial reports and multicenter studies on PI-based AMR treatment, including bortezomib.
• Analysis of case reports on PI as primary AMR therapy.
• Examination of recent studies on differential responses to PI in early and late post-transplant AMR.

Main Results:

• PI effectively depletes plasma cells producing DSAs.
• PI treatment leads to reduced DSA levels, histological improvement, and enhanced renal allograft function.
• PI demonstrates efficacy in both refractory and primary AMR cases.

Conclusions:

• Proteasome inhibition represents a significant advancement in AMR treatment, targeting mature antibody-producing plasma cells.
• Further randomized trials are investigating PI's role in various stages of renal transplant rejection.
• PI offers potential synergistic strategies for optimizing AMR therapy.