Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation
| Autor: | Kalathil K Sureshkumar, Carlos A Vivas, Ngoc Thai, Kusum Tom, George Parris, Sabiha M Hussain, Tina Y. Ko, Akhtar Khan, Katherine M. Jasnosz, Richard J. Marcus |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Graft Rejection Male Proteasome Endopeptidase Complex medicine.medical_specialty Biopsy medicine.medical_treatment Urology Renal function Severity of Illness Index Bortezomib chemistry.chemical_compound Isoantibodies hemic and lymphatic diseases medicine Humans Protease Inhibitors Kidney transplantation Creatinine business.industry General Medicine Middle Aged medicine.disease Boronic Acids Kidney Transplantation Transplantation Treatment Outcome chemistry Nephrology Pyrazines Proteasome inhibitor Cancer research Kidney Failure Chronic Female Plasmapheresis Rituximab business Proteasome Inhibitors medicine.drug |
| Zdroj: | Clinical Nephrology. 77:246-253 |
| ISSN: | 0301-0430 |
| Popis: | Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up. |
| Databáze: | OpenAIRE |
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