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Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

ABSTRACT: Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

PROVIDER: PRJNA607101 | ENA |

REPOSITORIES: ENA

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Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

Project description: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 While studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs. unsuccessful Tac removal are unknown.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.

2020-02-18 | GSE145408 | GEO

Cellular and Molecular Immune Profiles in Renal Transplant Recipients after Conversion from Tacrolimus to Sirolimus

Project description:Tacrolimus and Sirolimus are commonly used to maintain immunosuppression in kidney transplantation. However, their effects on immune cells and allograft molecular profiles have not been elucidated. Here we characterized the effects of Tacrolimus to Sirolimus conversion on frequency and function of T cells, and on graft molecular profiles. Samples from 30 renal transplant recipients in a randomized trial of late Sirolimus conversion (n=18) vs. Tacrolimus maintenance (n=12) were utilized. Peripheral blood was collected at 0- 6- 12 and 24-months post-randomization. This dataset only contains the 18 arrays corresponding to patients treated with Sirolimus.

2014-09-17 | E-GEOD-55998 | biostudies-arrayexpress

Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

Project description:Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

| PRJNA486227 | ENA

Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

Project description:Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

| PRJNA486228 | ENA

Kidney transplant recipients

Project description:Kidney transplant recipients

| PRJNA1054489 | ENA

Withdrawal of immunosuppressive therapy in stable liver transplant recipients

Project description:Complications due to long-term administration of immunosuppressive therapy increase the morbidity and mortality of liver transplant recipients. Discontinuation of immunosuppressive drugs in recipients spontaneously developing operational tolerance could substantially lessen this burden. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients. Methods. We enrolled 102 stable liver transplant recipients in an immunosuppression withdrawal trial in which drugs were gradually discontinued over a 6-9 month period. Patients with stable graft function and no signs of rejection in a liver biopsy conducted 12 months after cessation of immunosuppressive therapy were considered operationally tolerant. Results. Out of the 98 recipients who completed the study, immunosuppression discontinuation was successful in 41 recipients and rejection occurred in 57. Rejection episodes were mild and were resolved in all cases. Development of tolerance was independently associated with time elapsed since transplantation, recipient age, and male gender. No histological damage was apparent in protocol biopsies performed after successful drug withdrawal.

2012-01-09 | GSE28842 | GEO

Biomarkers in Transplant Recipients

Project description:Biomarkers in Transplant Recipients

| PRJNA290675 | ENA

Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients.

Project description: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.

| S-EPMC7704683 | biostudies-literature

Affymetrix SNP array data for kidney transplant samples

Project description:Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable inter-individual variability in pharmacokinetics (PK). Genetic and clinical factors play important roles in TAC PK. To define genetic factors associated with tacrolimus blood trough concentration, we performed a genome-wide association study of renal transplant samples from 251 Chinese renal transplant recipients. We identified 23 single nucleotide polymorphisms (SNPs) related to TAC PK variability. All 23 genome-wide significant SNPs (p<5E-8) were located on chromosome 7, including rs776746. These findings suggest that these SNPs may be associated with the unexlained TAC PK variability in renal transplant recipients and require further investigation.

2022-02-24 | GSE196772 | GEO

Cellular and Molecular Immune Profiles in Renal Transplant Recipients after Conversion from Tacrolimus to Sirolimus

2014-09-17 | GSE55998 | GEO