Proteasome Inhibition Reduces Donor-Specific Antibody Levels

M. J. Everly, J. J. Everly, B. Susskind, P. Brailey, Lois J Arend, R. R. Alloway, P. Roy-Chaudhury, A. Govil, G. Mogilishetty, A. H. Rike, M. Cardi, G. Wadih, E. Brown, A. Tevar, E. S. Woodle

Research output: Contribution to journalArticle

Abstract

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/m2 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.

Original languageEnglish (US)
Pages (from-to)105-107
Number of pages3
JournalTransplantation Proceedings
Volume41
Issue number1
DOIs
StatePublished - Jan 2009

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Proteasome Endopeptidase Complex
Tissue Donors
Antibodies
Anti-Idiotypic Antibodies
Plasma Cells
Fluorescence
Antibody-Producing Cells
Blood Component Removal
Plasmacytoma
Intravenous Immunoglobulins
Opportunistic Infections
United States Food and Drug Administration
Therapeutics
Cell- and Tissue-Based Therapy
Bortezomib
Multiple Myeloma
Nausea
Vomiting
Diarrhea
B-Lymphocytes

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Everly, M. J., Everly, J. J., Susskind, B., Brailey, P., Arend, L. J., Alloway, R. R., ... Woodle, E. S. (2009). Proteasome Inhibition Reduces Donor-Specific Antibody Levels. Transplantation Proceedings, 41(1), 105-107. https://doi.org/10.1016/j.transproceed.2008.10.073

Proteasome Inhibition Reduces Donor-Specific Antibody Levels. / Everly, M. J.; Everly, J. J.; Susskind, B.; Brailey, P.; Arend, Lois J; Alloway, R. R.; Roy-Chaudhury, P.; Govil, A.; Mogilishetty, G.; Rike, A. H.; Cardi, M.; Wadih, G.; Brown, E.; Tevar, A.; Woodle, E. S.

In: Transplantation Proceedings, Vol. 41, No. 1, 01.2009, p. 105-107.

Research output: Contribution to journalArticle

Everly, MJ, Everly, JJ, Susskind, B, Brailey, P, Arend, LJ, Alloway, RR, Roy-Chaudhury, P, Govil, A, Mogilishetty, G, Rike, AH, Cardi, M, Wadih, G, Brown, E, Tevar, A & Woodle, ES 2009, 'Proteasome Inhibition Reduces Donor-Specific Antibody Levels', Transplantation Proceedings, vol. 41, no. 1, pp. 105-107. https://doi.org/10.1016/j.transproceed.2008.10.073
Everly, M. J. ; Everly, J. J. ; Susskind, B. ; Brailey, P. ; Arend, Lois J ; Alloway, R. R. ; Roy-Chaudhury, P. ; Govil, A. ; Mogilishetty, G. ; Rike, A. H. ; Cardi, M. ; Wadih, G. ; Brown, E. ; Tevar, A. ; Woodle, E. S. / Proteasome Inhibition Reduces Donor-Specific Antibody Levels. In: Transplantation Proceedings. 2009 ; Vol. 41, No. 1. pp. 105-107.
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abstract = "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/m2 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.",
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AU - Everly, M. J.

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AU - Susskind, B.

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AU - Arend, Lois J

AU - Alloway, R. R.

AU - Roy-Chaudhury, P.

AU - Govil, A.

AU - Mogilishetty, G.

AU - Rike, A. H.

AU - Cardi, M.

AU - Wadih, G.

AU - Brown, E.

AU - Tevar, A.

AU - Woodle, E. S.

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N2 - 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/m2 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.

AB - 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/m2 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.

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