0 23

Cited 0 times in

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

Authors
 Wiebke Sommer  ;  Jane M O  ;  Kurt B Pruner  ;  Abbas Dehnadi  ;  Kyu Ha Huh  ;  Kortney A Robinson  ;  Isabel Hanekamp  ;  Ivy Rosales  ;  Alison S Bean  ;  Josh Paster  ;  Tetsu Oura  ;  Rex Neal Smith  ;  Robert Colvin  ;  Gilles Benichou  ;  Tatsuo Kawai  ;  Joren C Madsen  ;  James S Allan 
Citation
 TRANSPLANTATION DIRECT, Vol.7(6), 2021-05 
Journal Title
TRANSPLANTATION DIRECT
Issue Date
2021-05
Abstract
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.
DOI
10.1097/TXD.0000000000001150
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190927
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links