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Series GSE145408 Query DataSets for GSE145408
Status Public on Feb 18, 2020
Title Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. While studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs. unsuccessful Tac removal are unknown.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 PBMC RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which stable kidney transplant recipients were randomized to Tac withdrawal or maintenance of standard immunosuppression beginning 6-mo post-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 distinct, T cell-specific, downregulatory, and pro-apoptotic gene program. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data suggest that successful Tac withdrawal can unleash an active, protective pro-apoptotic T cell program, and provide the foundation for developing strategies to promote this protective immunological phenotype in kidney transplant recipients.
 
Overall design Samples of PBMCs obtained from patients 6 months post kidney transplant randomized to no withdrawal (N=4) and Tac withdrawal (N=14), and 3 months post Tac withdrawal when tapering was completed. See PMID: 25925687 for more references.
 
Contributor(s) Fribourg M, Cravedi P, Heeger PS
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Submission date Feb 17, 2020
Last update date Feb 21, 2020
Contact name Miguel Fribourg
E-mail(s) Miguel.Fribourg@mssm.edu
Phone 212-241-4534
Organization name Icahn School of Medicine at Mount Sinai
Department Medicine
Street address 1 Gustave Levy Pl
City New York
State/province NY
ZIP/Postal code 10029
Country USA
 
Platforms (1)
GPL13158 [HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate
Samples (36)
GSM4317771 patient 1001 6 mo post tx pre Tac w/d
GSM4317772 patient 1001 9 mo post tx 3mo post Tac w/d
GSM4317773 patient 4006 6 mo post tx pre Tac w/d
Relations
BioProject PRJNA607101

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Supplementary file Size Download File type/resource
GSE145408_RAW.tar 72.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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