A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

Autor:	Sommer W; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany., O JM; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Pruner KB; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Dehnadi A; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.; Department of Transplantation Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA.; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Division of Cardiac Surgery, Massachusetts General Hospital, Boston, MA.; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA., Ha Huh K; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Department of Transplantation Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea., Robinson KA; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA., Hanekamp I; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Rosales I; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Bean AS; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Paster J; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Oura T; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Neal Smith R; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Colvin R; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Benichou G; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Kawai T; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Madsen JC; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Division of Cardiac Surgery, Massachusetts General Hospital, Boston, MA., Allan JS; Center for Transplantation Science, Massachusetts General Hospital and Harvard Medical School, Boston, MA.; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA.
Jazyk:	angličtina
Zdroj:	Transplantation direct [Transplant Direct] 2021 May 25; Vol. 7 (6), pp. e705. Date of Electronic Publication: 2021 May 25 (Print Publication: 2021).
DOI:	10.1097/TXD.0000000000001150
Abstrakt:	Background: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts. Methods: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT. Results: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients. Conclusion: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction. Competing Interests: W.S. received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) -SO 1519/1-1. The other authors declare no conflicts of interest. (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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