Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons..
Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. Although studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs unsuccessful Tac removal are unknown. We performed microarray analyses of peripheral blood mononuclear cells (PBMC) RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which we randomized stable kidney transplant recipients to Tac withdrawal or maintenance of standard immunosuppression beginning 6 months after transplant. Eight of 14 subjects attempted but failed withdrawal, while six developed stable graft function for ≥2 years on mycophenolate mofetil plus prednisone. Whereas failed withdrawal upregulated immune activation genes, successful Tac withdrawal was associated with a downregulatory and proapoptotic gene program enriched within T cells. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data from a small, but unique, patient cohort support the conclusion that successful Tac withdrawal is not simply due to absence of donor-reactive immunity but rather is associated with an active immunological process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - 20(2020), 12 vom: 07. Dez., Seite 3477-3485 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cravedi, Paolo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.05.2021 Date Revised 24.01.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/ajt.15979 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31041055X |
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| 245 | 1 | 0 | |a Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients |
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| 520 | |a © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons. | ||
| 520 | |a Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. Although studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs unsuccessful Tac removal are unknown. We performed microarray analyses of peripheral blood mononuclear cells (PBMC) RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which we randomized stable kidney transplant recipients to Tac withdrawal or maintenance of standard immunosuppression beginning 6 months after transplant. Eight of 14 subjects attempted but failed withdrawal, while six developed stable graft function for ≥2 years on mycophenolate mofetil plus prednisone. Whereas failed withdrawal upregulated immune activation genes, successful Tac withdrawal was associated with a downregulatory and proapoptotic gene program enriched within T cells. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data from a small, but unique, patient cohort support the conclusion that successful Tac withdrawal is not simply due to absence of donor-reactive immunity but rather is associated with an active immunological process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a immunobiology | |
| 650 | 4 | |a immunosuppressant - calcineurin inhibitor: tacrolimus | |
| 650 | 4 | |a immunosuppression/immune modulation | |
| 650 | 4 | |a kidney (allograft) function/dysfunction | |
| 650 | 4 | |a translational research/science | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Mycophenolic Acid |2 NLM | |
| 650 | 7 | |a HU9DX48N0T |2 NLM | |
| 650 | 7 | |a Tacrolimus |2 NLM | |
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| 700 | 1 | |a Fribourg, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weijia |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Zhengzi |e verfasserin |4 aut | |
| 700 | 1 | |a Zaslavsky, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Nudelman, German |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Hartzell, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Brouard, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Heeger, Peter S |e verfasserin |4 aut | |
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