Proteasome inhibition reduces donor-specific antibody levels
| Autor: | Prabir Roy-Chaudhury, Amit Govil, Lois J. Arend, E. S. Woodle, Matthew J Everly, Paul Brailey, Evan A. Brown, Rita R. Alloway, G. Mogilishetty, A.H. Rike, M. Cardi, J. J. Everly, Amit D. Tevar, G Wadih, B. Susskind |
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| Rok vydání: | 2008 |
| Předmět: |
Graft Rejection
medicine.medical_specialty medicine.medical_treatment Plasma cell Gastroenterology Targeted therapy Bortezomib immune system diseases Isoantibodies hemic and lymphatic diseases Internal medicine medicine Humans Protease Inhibitors Multiple myeloma Transplantation biology business.industry medicine.disease Boronic Acids Kidney Transplantation medicine.anatomical_structure Pyrazines Immunology Proteasome inhibitor biology.protein Surgery Rituximab Pancreas Transplantation Antibody business Proteasome Inhibitors medicine.drug Follow-Up Studies |
| Zdroj: | Transplantation proceedings. 41(1) |
| ISSN: | 0041-1345 |
| Popis: | Background Current antibody-mediated rejection (AMR) therapies (intravenous immunoglobulin, apheresis, rituximab, polyclonal antibodies) do not target the primary antibody producing B cells, that is, the plasma cell. We report the preliminary results from the first clinical experience with plasma cell targeted therapy with bortezomib. Bortezomib is approved by the US Food and Drug Administration for the treatment of plasma cell tumors (multiple myeloma). Methods Kidney transplant patients with mixed acute cellular rejection (ACR) and AMR episodes (by Banff ‘97 criteria, update 2005) were treated with bortezomib (1.3 mg/m 2 per dose × 4) at standard labeled doses. Patients were monitored by serial donor specific anti-HLA antibody (DSA) determinations [Luminex/Labscreen beads] and quantified by conversion to fluorescence intensity to molecules of equivalent soluble fluorescence (MESF). Results Five patients were treated with bortezomib. Each patient also had coexisting ACR. In each case, bortezomib treatment led to prompt ACR and AMR rejection reversal. DSA levels decreased significantly in all patients (except 1 patient who had short follow-up). Observed toxicities from bortezomib included a transient grade III thrombocytopenia (1 patient) and mild-to-moderate nausea, vomiting, and/or diarrhea (3/5 patients). Opportunistic infections were not observed. Conclusions Bortezomib therapy provides effective reduction in DSA levels with long-term suppression. These preliminary results indicate that proteasome inhibition provides an effective means for reducing HLA antibody levels in transplant recipients. |
| Databáze: | OpenAIRE |
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