Proteasome inhibition reduces donor-specific antibody levels

Area of Science:

• Transplantation immunology
• Nephrology
• Oncology therapeutics

Background:

• Current antibody-mediated rejection (AMR) therapies do not target plasma cells, the primary source of antibodies.
• Bortezomib, a proteasome inhibitor, is FDA-approved for multiple myeloma and targets plasma cells.

Purpose of the Study:

• To evaluate the preliminary clinical experience of bortezomib for targeted plasma cell therapy in kidney transplant recipients.
• To assess the efficacy of bortezomib in reducing donor-specific anti-HLA antibody (DSA) levels during rejection episodes.

Main Methods:

• Five kidney transplant patients with mixed acute cellular rejection (ACR) and AMR were treated with bortezomib (1.3 mg/m(2) x 4 doses).
• Patients were monitored for DSA levels using Luminex assays, quantified by fluorescence intensity.

Main Results:

• Bortezomib treatment led to prompt reversal of ACR and AMR in all patients.
• Significant decreases in DSA levels were observed in most patients.
• Observed toxicities included transient thrombocytopenia and gastrointestinal upset; no opportunistic infections occurred.

Conclusions:

• Bortezomib therapy effectively reduces DSA levels with sustained suppression in kidney transplant recipients.
• Proteasome inhibition with bortezomib presents a promising strategy for managing antibody-mediated rejection by targeting plasma cells.