Affymetrix SNP array data for kidney transplant samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196772 | GEO | 2022/02/24
REPOSITORIES: GEO
Similar Datasets
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 While studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs. unsuccessful Tac removal are unknown.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
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
Project description:Following liver transplantation, the liver function of a patient is gradually restored over a period of time, which is divided into a convalescence period (CP) and a stabilizing period (SP). Tacrolimus (TAC), a commonly-used immunosuppressant for the prevention of organ rejection, shows variability in plasma concentration in these patients as a result of variation in its metabolism. The effects of genetic and clinical factors on its plasma levels seem to differ in the CP and SP. To establish a model explaining TAC trough concentration variation between individuals in both the CP and SP, we conducted a retrospective, single-center, discovery study, involving 115 pairs of patients (115 donors and 115 matched recipients) who had undergone liver transplantation. Donors and recipients were genotyped by genomewide association study (GWAS) using an exome chip.
2019-04-29 | GSE130068 | GEO
Project description:Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients.
2013-04-01 | GSE45593 | GEO
Project description:Chronic calcineurin inhibitor (CNI) nephrotoxicity is a major drawback in current immunosuppressive regimens. Pathology includes vascular and tubulointerstitial alterations. Although still commonly in use, cyclosporine A (CsA) is increasingly exchanged for tacrolimus (Tac) for a more favorable clinical outcome. Data on their differential pathogenetic effects in the kidney are, however, still scarce. We asked how CsA and Tac may affect adverse renal responses differentially. Methods- Wistar rats were divided into groups receiving cyclosporineÊ AÊ (n=4, target trough plasma level 3 mg/ml) and the respective vehicle (n=4, saline), or tacrolimus (Tac, FK506, n= 6, target trough plasma level 3.5 ng/ml) and the respective vehicle (n=6, DMSO/PEG500), via subcutaneously implanted osmotic minipumps for 28 days. Clinical parameters from plasma and urine samples were controlled. Animals were prepared for high-end morphological analysis, elective immunostaining, and high-throughput technology. Large scale electron microscopy (EM), confocal, stimulated emission-depletion (STED) and 3D-structured illumination (SIM) microscopy were used for pathology. Protein biochemistry, transcriptome, proteome, and phosphoproteome technologies were used to identify gene expressional differences. Results - In rats, CsA and Tac produced common as well as distinct alterations in glomeruli and tubulointerstitium. Both drugs caused cortical fibrotic foci with sclerotic glomeruli and damaged tubules. With CsA, glomerular damage was milder than with Tac. Proximal tubules showed widespread dysmorphic lysosomes with peripheral LAMP1 signal as well as autophagic and mitophagic vacuoles along with high apoptosis rate and diminished albumin uptake; megalin-dependent endocytosis was causally involved in the changes, and lysosomal exocytosis was sharply stimulated at the luminal cell pole. KIM1 signal was moderate. With Tac, these changes were far less pronounced, but the incidence of focal tubular necrosis along with intense KIM-1 signal was high. High throughput analysis showed differential changes between CsA and Tac with almost no overlap between the respective spectra. CsA caused upregulation of components of the unfolded protein response and apoptosis, whereas Tac resulted in RAS-associated stimulation and vascular deterioration. Conclusions- CNI nephrotoxicity presented with widely differing pathogenetic characteristics upon chronical CsA vs. Tac treatments. Beyond its known vascular effects, CsA markedly affected proximal tubular integrity, whereas Tac was primarily affecting vascular/glomerular components. Both medications produced comparable degrees of nephron loss and fibrosis. Results may serve to better adjust immunosuppressive treatment combinations in transplant patients.
2024-07-25 | PXD038546 | Pride
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
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft.
2017-09-01 | GSE83486 | GEO
Project description:We previously observed reduced graft survival for kidney transplants having interstitial fibrosis with subclinical inflammation, but not fibrosis alone, on 1-year protocol biopsy. The current study aimed to determine whether fibrosis with inflammation at 1 year is associated with renal functional decline in a low-risk transplant cohort and to characterize the nature of the inflammation. Subjects were living-donor, tacrolimus/mycophenolate-treated transplant recipients without overt risk factors for reduced graft survival (n=151). Transplants with normal histology (n=86) or fibrosis alone (n=45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, while those having fibrosis with inflammation (n=20) had declining glomerular filtration rate and reduced graft survival. Immunohistochemistry confirmed increased interstitial T-cells and macrophages/dendritic cells in the fibrosis with inflammation group. Gene expression was performed on a subset of biopsies in each group and demonstrated increased expression of transcripts related to innate and cognate immunity in transplants having fibrosis with inflammation. Pathway- and pathological process-specific analyses of microarray profiles revealed that, in fibrosis with inflammation, over-expressed transcripts were enriched for potentially damaging immunological activities including Toll-like receptor signaling, antigen presentation/dendritic cell maturation, interferon gamma-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes. Thus, fibrosis with inflammation in 1-year protocol biopsies is associated with reduced graft survival and function and with a rejection-like gene expression signature even in recipients with no clinical risk for inferior outcome. Early interventions aimed at altering rejection-like inflammation may favor improved long-term KTx survival. We analyzed gene expression from a group of 65 renal transplant recipients. Patient groups were carefully selected to include patients on the same immunosuppression (Prograf-MMF-Pred), transplant type (LD), absence of over post-transplant complications (AR, BK, DGF). For each patient a 1 year protocol biopsy was examined by conventional histology and gene expression. By histology the patients were categorized as histologically normal (n=25, i/cg/ci=0), IF/TA (n=24, i/cg=0, ci>0) and IFTA+i (n=16, cg=0, i/ci>0). This dataset is part of the TransQST collection.
2010-11-01 | E-GEOD-22459 | biostudies-arrayexpress
Project description:Cellular and Molecular Immune Profiles in Renal Transplant Recipients after Conversion from Tacrolimus to Sirolimus
| PRJNA242138 | ENA
Project description:Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients. A total of 46 PBMC samples representing blood draws from four time points in the first 9 recipients were processed for microarray analysis (The Scripps Research Institute, La Jolla, CA). The analyzed time points were: immediately pre-operatively in the absence of immunosuppression (n=9); post-operatively at 1 year (n=8, range 11-13 months); at 2 years (n=12, range 18-25 months); >3 years (n=17, range 32-48 months). (At year 2 and at > 3 years, repeated samples were obtained from individual subjects, and at one year, one subject had a technically unsatisfactory sample.) To discount the effects of immunosuppression on gene expression, microarray data were included on whole blood from 18 healthy human subjects (controls: GSE40586; NCBI Gene Expression Omnibus [GEO] repository).
2013-04-01 | E-GEOD-45593 | biostudies-arrayexpress