A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation
| العنوان: | A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation |
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| المؤلفون: | Kurt B Pruner, I.M. Hanekamp, James S. Allan, Tatsuo Kawai, Joren C. Madsen, Alison S Bean, Ivy A. Rosales, Jane M O, Josh Paster, A. Dehnadi, Gilles Benichou, T. Oura, Wiebke Sommer, Kortney A. Robinson, Kyu Ha Huh, Robert B. Colvin, Rex Neal Smith |
| المصدر: | Transplantation Direct Transplantation Direct, Vol 7, Iss 6, p e705 (2021) |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | RD1-811, medicine.medical_treatment, 030230 surgery, Belatacept, 03 medical and health sciences, 0302 clinical medicine, medicine, Lung transplantation, Kidney transplantation, Transplantation, Kidney, Thymoglobulin, business.industry, Immunosuppression, medicine.disease, Tolerance induction, surgical procedures, operative, medicine.anatomical_structure, Immunology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Surgery, 030211 gastroenterology & hepatology, business, Lung Transplantation, medicine.drug |
| الوصف: | Supplemental Digital Content is available in the text. 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. |
| تدمد: | 2373-8731 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9559c3ea369c2623c193f0c355424ba6 https://doi.org/10.1097/txd.0000000000001150 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9559c3ea369c2623c193f0c355424ba6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23738731 |
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