Novel pretransplant desensitization strategies in heart transplantation
Allosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rej...
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Elsevier
2025-05-01
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| Series: | JHLT Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133425000370 |
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| author | Guillaume Coutance, MD, PhD Anita S. Chong, PhD Marlena V. Habal, MD |
| author_facet | Guillaume Coutance, MD, PhD Anita S. Chong, PhD Marlena V. Habal, MD |
| author_sort | Guillaume Coutance, MD, PhD |
| collection | DOAJ |
| description | Allosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rejection have been developed, but current strategies have limited efficacy, and new strategies are needed. After a synthetic description of the basics of alloimmune responses leading to the production of donor-specific antibodies, the potential of novel desensitization strategies, including anti-CD38 therapies, costimulation blockade, and interleukin-6 inhibition as pretransplant desensitization therapies, are discussed in detail, including the rationale for their use, results of preclinical and clinical studies, and potential practical clinical application. Complementary novel pharmacologic (individualization therapies, combination desensitization therapies, additional perioperative antibody-risk mitigation strategies) and nonpharmacologic strategies (individual risk stratification and combination of immunologic assays) are also presented. Finally, potential next-generation therapies (bispecific T-cell engager and chimeric antigen receptor T cells) and clinical outcomes of interest are briefly discussed. Overall, this review aims to provide recent data on this constantly evolving field, while keeping in mind the clinical applicability and providing practical aspects of the use of novel pretransplant desensitization therapies. |
| format | Article |
| id | doaj-art-856f06aa164f4f1dbe45e45b6a8b63ad |
| institution | Kabale University |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHLT Open |
| spelling | doaj-art-856f06aa164f4f1dbe45e45b6a8b63ad2025-08-20T03:48:50ZengElsevierJHLT Open2950-13342025-05-01810024210.1016/j.jhlto.2025.100242Novel pretransplant desensitization strategies in heart transplantationGuillaume Coutance, MD, PhD0Anita S. Chong, PhD1Marlena V. Habal, MD2Department of Cardiac and Thoracic Surgery, Cardiology Institute, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University Medical School, Paris, France; Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, University Paris Cité, Paris, France; Corresponding author: Guillaume Coutance, MD, PhD, Service de Chirurgie Cardiaque, GH Pitié-Salpêtrière, 56, Bd Vincent Auriol, 75013 Paris, France.Department of Surgery, University of Chicago, Chicago, IllinoisDivision of Cardiology, Department of Medicine, New York University, Grossman School of Medicine, New York, New YorkAllosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rejection have been developed, but current strategies have limited efficacy, and new strategies are needed. After a synthetic description of the basics of alloimmune responses leading to the production of donor-specific antibodies, the potential of novel desensitization strategies, including anti-CD38 therapies, costimulation blockade, and interleukin-6 inhibition as pretransplant desensitization therapies, are discussed in detail, including the rationale for their use, results of preclinical and clinical studies, and potential practical clinical application. Complementary novel pharmacologic (individualization therapies, combination desensitization therapies, additional perioperative antibody-risk mitigation strategies) and nonpharmacologic strategies (individual risk stratification and combination of immunologic assays) are also presented. Finally, potential next-generation therapies (bispecific T-cell engager and chimeric antigen receptor T cells) and clinical outcomes of interest are briefly discussed. Overall, this review aims to provide recent data on this constantly evolving field, while keeping in mind the clinical applicability and providing practical aspects of the use of novel pretransplant desensitization therapies.http://www.sciencedirect.com/science/article/pii/S2950133425000370heart transplantationdesensitizationantibody-mediated rejectionimmunosuppressionimmunology |
| spellingShingle | Guillaume Coutance, MD, PhD Anita S. Chong, PhD Marlena V. Habal, MD Novel pretransplant desensitization strategies in heart transplantation JHLT Open heart transplantation desensitization antibody-mediated rejection immunosuppression immunology |
| title | Novel pretransplant desensitization strategies in heart transplantation |
| title_full | Novel pretransplant desensitization strategies in heart transplantation |
| title_fullStr | Novel pretransplant desensitization strategies in heart transplantation |
| title_full_unstemmed | Novel pretransplant desensitization strategies in heart transplantation |
| title_short | Novel pretransplant desensitization strategies in heart transplantation |
| title_sort | novel pretransplant desensitization strategies in heart transplantation |
| topic | heart transplantation desensitization antibody-mediated rejection immunosuppression immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2950133425000370 |
| work_keys_str_mv | AT guillaumecoutancemdphd novelpretransplantdesensitizationstrategiesinhearttransplantation AT anitaschongphd novelpretransplantdesensitizationstrategiesinhearttransplantation AT marlenavhabalmd novelpretransplantdesensitizationstrategiesinhearttransplantation |