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Published on: September 10, 2018
Proteasome inhibition for antibody-mediated rejection
Jason J Everly1, R Carlin Walsh, Rita R Alloway
1Department of Surgery, University of Cincinnati College of Medicine, Ohio, USA.
Current Opinion in Organ Transplantation
|August 12, 2009
Summary
Proteasome inhibition therapy, including bortezomib, effectively targets plasma cells to treat antibody-mediated rejection in organ transplantation. This approach reduces donor-specific antibodies and shows promise for improving transplant outcomes.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Medicine
Background:
- Traditional therapies fail to deplete antibody-producing plasma cells.
- Proteasome inhibition offers a novel mechanism to target plasma cells.
Purpose of the Study:
- To review the biochemistry and physiology of proteasome inhibition.
- To discuss proteasome inhibitor therapy in organ transplantation.
Main Methods:
- Review of preclinical and clinical studies on proteasome inhibitors.
- Analysis of bortezomib's effects on plasma cells and antibody levels.
Main Results:
- Proteasome inhibition depletes both normal and malignant plasma cells.
- Bortezomib effectively treats antibody-mediated rejection and reduces donor-specific antibodies in kidney transplant recipients.
- Bortezomib can reduce donor-specific antibodies even without active rejection.
Conclusions:
- Proteasome inhibition has pleiotropic effects, particularly on plasma cells.
- Bortezomib shows efficacy in treating rejection and reducing donor-specific antibodies.
- Further clinical trials are necessary to establish the definitive role of proteasome inhibition in transplantation.
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