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The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report

BACKGROUND: Antibody-mediated rejection (AMR) remains a major management challenge in heart transplantation given the complexity of pathological diagnosis and dearth of evidence for effective management. Eculizumab, an anti-C5 monoclonal antibody which inhibits terminal complement activation, has be...

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Autores principales: Kearney, Katherine, Macdonald, Peter, Hayward, Christopher, Muthiah, Kavitha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110694/
https://www.ncbi.nlm.nih.gov/pubmed/33997604
http://dx.doi.org/10.1093/ehjcr/ytab180
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author Kearney, Katherine
Macdonald, Peter
Hayward, Christopher
Muthiah, Kavitha
author_facet Kearney, Katherine
Macdonald, Peter
Hayward, Christopher
Muthiah, Kavitha
author_sort Kearney, Katherine
collection PubMed
description BACKGROUND: Antibody-mediated rejection (AMR) remains a major management challenge in heart transplantation given the complexity of pathological diagnosis and dearth of evidence for effective management. Eculizumab, an anti-C5 monoclonal antibody which inhibits terminal complement activation, has been reported to decrease early AMR in sensitized renal transplant recipients. CASE SUMMARY: We report a case of a 29-year-old gentleman with chronic AMR 8 years after heart transplantation, manifesting as significant graft dysfunction. Donor-specific antibodies to DQ7 were found to be causative. Antibody-mediated rejection was managed with quadruple oral immunosuppressive therapy (mycophenolate, prednisolone, everolimus, and tacrolimus) as well as a sequence of broad-spectrum immunological therapies; intravenous (IV) methylprednisolone, plasmapheresis, IV immunoglobulin, rituximab, bortezomib, tocilizumab, and splenic irradiation. No treatment had a sustained impact on donor-specific anti-HLA antibodies (DSAs) or graft function. After testing showed the DQ7 antibodies were complement-binding, a trial of eculizumab was started. This improved DSAs somewhat, and improved graft function and New York Heart Association functional class substantially. The patient was relisted for heart transplantation and successfully retransplanted in March 2018. Specifically, the new organ and recipient were matched at DQ7. After discontinuation of eculizumab, the patient has remained healthy and well, with normal graft function 28 months after retransplantation. DISCUSSION: To the best of our knowledge, this is the first case of chronic AMR in a heart transplant patient, successfully stabilized with eculizumab and bridged to retransplantation.
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spelling pubmed-81106942021-05-13 The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report Kearney, Katherine Macdonald, Peter Hayward, Christopher Muthiah, Kavitha Eur Heart J Case Rep Case Report BACKGROUND: Antibody-mediated rejection (AMR) remains a major management challenge in heart transplantation given the complexity of pathological diagnosis and dearth of evidence for effective management. Eculizumab, an anti-C5 monoclonal antibody which inhibits terminal complement activation, has been reported to decrease early AMR in sensitized renal transplant recipients. CASE SUMMARY: We report a case of a 29-year-old gentleman with chronic AMR 8 years after heart transplantation, manifesting as significant graft dysfunction. Donor-specific antibodies to DQ7 were found to be causative. Antibody-mediated rejection was managed with quadruple oral immunosuppressive therapy (mycophenolate, prednisolone, everolimus, and tacrolimus) as well as a sequence of broad-spectrum immunological therapies; intravenous (IV) methylprednisolone, plasmapheresis, IV immunoglobulin, rituximab, bortezomib, tocilizumab, and splenic irradiation. No treatment had a sustained impact on donor-specific anti-HLA antibodies (DSAs) or graft function. After testing showed the DQ7 antibodies were complement-binding, a trial of eculizumab was started. This improved DSAs somewhat, and improved graft function and New York Heart Association functional class substantially. The patient was relisted for heart transplantation and successfully retransplanted in March 2018. Specifically, the new organ and recipient were matched at DQ7. After discontinuation of eculizumab, the patient has remained healthy and well, with normal graft function 28 months after retransplantation. DISCUSSION: To the best of our knowledge, this is the first case of chronic AMR in a heart transplant patient, successfully stabilized with eculizumab and bridged to retransplantation. Oxford University Press 2021-05-11 /pmc/articles/PMC8110694/ /pubmed/33997604 http://dx.doi.org/10.1093/ehjcr/ytab180 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Case Report
Kearney, Katherine
Macdonald, Peter
Hayward, Christopher
Muthiah, Kavitha
The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title_full The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title_fullStr The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title_full_unstemmed The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title_short The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
title_sort use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110694/
https://www.ncbi.nlm.nih.gov/pubmed/33997604
http://dx.doi.org/10.1093/ehjcr/ytab180
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