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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Catherine Dumur

PROVIDER: E-GEOD-55998 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

2014-09-17 | GSE55998 | GEO

Tacrolimus- and sirolimus-induced human b cell dysfunction is reversible and preventable

Project description:We used RNA-seq to investigate transcriptional changes in human islet grafts that were treated in vivo with tacrolimus or sirolimus. We show that this treatment induces broad transcriptional dysregulation related to peptide processing, ion/calcium flux, and the extracellular matrix.

2020-01-31 | GSE140230 | GEO

Sirolimus induced phosphaturia

Project description:Introduction: The kidney is the major arbiter of extracellular phosphate homeostasis. The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal tubule. Posttransplant phosphaturia is common and aggravated by sirolimus immunosuppression. The cause of sirolimus induced phosphaturia however remains elusive. Results: The urine phosphate/creatinine ratio was higher and serum phosphate was lower in sirolimus treated rats, fractional excretion of phosphate was elevated and renal tubular phosphate reabsorption was reduced suggesting a renal cause for hypophosphatemia. PTH was lower in sirolimus treated rats. FGF 23 levels were unchanged at day 2 but lower in sirolimus treated rats after 7 days. Brush border membrane vesicle phosphate uptake was not altered in sirolimus treated groups or by direct incubation with sirolimus. mRNA, protein abundance, and subcellular transporter distribution of NaPi-IIa, Pit-2 and NHE3 were not different between groups but NaPi-IIc mRNA expression was lower at day 7. Transcriptome analyses revealed candidate genes that could be involved in the phosphaturic response. Discussion: Sirolimus caused a selective renal phosphate leakage which was not mediated by NaPi-IIa or NaPi-IIc regulation or localization. We hypothesize that another mechanism such as a basolateral phosphate transporter may be responsible for the sirolimus induced phosphaturia. Male Wistar rats received sirolimus or vehicle for 7 days (1.5mg/kg) and were placed in individual metabolic cages for eight days allowing a 24 hour adaption period to the metabolic cage environment. At the end of the experiments rats were anesthetized by inhalation of Isoflurane/air and blood samples and kidneys were collected. 4 cases (sirolimus) and 4 controls (vehicle) have been analysed

2012-09-24 | E-GEOD-35048 | biostudies-arrayexpress

Sirolimus induced phosphaturia

2012-09-24 | GSE35048 | GEO

Tacrolimus- and sirolimus-induced human b cell dysfunction is reversible and preventable

Project description:Tacrolimus- and sirolimus-induced human b cell dysfunction is reversible and preventable

| PRJNA588996 | ENA

Molecular Profiles Associated with Calcineurin Inhibitor Toxicity Post-Kidney Transplant: Input to Chronic Allograft Dysfunction

Project description:The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated. Molecular signatures characterizing CNIT samples were identified. The recognized CNIT gene signature was most common in patients with decreased graft function and histological evidence of IF/TA. To test CNIT contribution to CAD progression, kidney biopsies from transplant recipients with histological diagnosis of CNIT (n=14), acute rejection (ACR, n=13), and CAD with IF/TA (n=10), including 18 Normal allografts, were analyzed using gene expression microarrays.

2014-06-01 | E-GEOD-53605 | biostudies-arrayexpress

Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus

2008-11-20 | E-GEOD-12024 | biostudies-arrayexpress

Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

Project description:RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient’s immune system from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

| 2048717 | ecrin-mdr-crc

B lymphocytes signature is associated with the success of minimization therapy in kidney transplantation

Project description:The efficacy and safety of tacrolimus or sirolimus monotherapy after combined induction therapy with campath-1H and infliximab monoclonal antibodies in 20 kidney graft recipients were evaluated in single centre prospective randomized trial. Campath-1H and infliximab induction followed by tacrolimus monotherapy spare tolerance asssociated naive B-cell related molecular markers and results in 36 months excellent renal graft function and normal histology.

2017-02-16 | GSE39299 | GEO

Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients under Cyclosporin A or Sirolimus Monotherapy

Project description:Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation. The complete database comprised the expression measurements of 54 675 genes for kidney trasplant recipient PBMC treated with SRL (n=23) and CSA (n=14) monotherapy. 9 healthy controls were also included.

2010-10-01 | E-GEOD-22224 | biostudies-arrayexpress

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