Transcriptomics,Genomics

Dataset Information

49

Immunosuppressive Drug-Free Operational Immune Tolerance in Human Kidney Transplant Recipients: Blood Gene Expression Analysis Tolerance in Human Kidney Transplant Recipients.


ABSTRACT: Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous ‘‘operational tolerance’’ can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation. 250 samples were analyzed, replicates included: some patients from the TOL and CR groups were sampled twice with an interval between the two different time points of at least 16 months (mean 25.8 months, range 16–31 months). All the samples were analyzed in duplicate or quadruplicate. 1. TOL (n = 21). patients with stable graft function (blood creatinemia<150 mmol/L, proteinuria<1 g/24 h) for at least 1 year (mean 6.4 years,range 1.6–17.2 years) after complete interruption of immunosuppressive therapy. 2. STA (n = 190). Patients with stable kidney graft function under immunosuppressive therapy. 3. CR (n = 31). Patients having a progressive degradation of their renal function (blood creatinemia ≥150 mmol/L, proteinuria ≥1 g/24 h). CR was diagnosed on a graft biopsy according to the updated Banff criteria. CR was defined by histological signs of chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear cell infiltration) and/or transplant glomerulopathy with glomerular double contours. 4. HV (n = 8). Subjects having normal blood formulae and no infectious or other concomitant pathology for at least 6 months before the study. Overall design: 250 PBMC (Peripheral Blood Mononuclear Cells) samples from 4 groups (TOL, STA, CR, HV) were analyzed by microarray.

REANALYSED by: GSE49198

INSTRUMENT(S): Human oligo array from MWG cancerochips_v2009

SUBMITTER: Daniel BARON  

PROVIDER: GSE47755 | GEO | 2017-02-09

SECONDARY ACCESSION(S): PRJNA212316

REPOSITORIES: GEO

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Publications

Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis.

Braud Christophe C   Baeten Dominique D   Giral Magali M   Pallier Annaïck A   Ashton-Chess Joanna J   Braudeau Cecile C   Chevalier Catherine C   Lebars Alice A   Léger Jean J   Moreau Anne A   Pechkova Eugenia E   Nicolini Claudio C   Soulillou Jean-Paul JP   Brouard Sophie S  

Journal of cellular biochemistry 20080401 6


Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous "operational tolerance" can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potent  ...[more]

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